Development of Therapeutics That Induce Mitochondrial Biogenesis for the Treatment of Acute and Chronic Degenerative Diseases

Journal of Medicinal Chemistry

Volumn 59, Issue 23, 2016, Pages 10411-10434

  Cameron, Robert B ^a,b   Beeson, Craig C ^a   Schnellmann, Rick G ^a,b  

^a MEDICAL UNIVERSITY OF SOUTH CAROLINA   (United States)

^b UNIVERSITY OF ARIZONA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

1,4 DIAMINO 1,4 BIS(2 AMINOPHENYLTHIO) 2,3 DICYANOBUTADIENE; 2,4 THIAZOLIDINEDIONE DERIVATIVE; 3,3 BIS(2 AMINOETHYL) 1 HYDROXY 2 OXOTRIAZENE; 5 AMINO 4 IMIDAZOLECARBOXAMIDE RIBOSIDE; 6,7 DIHYDRO 4 HYDROXY 3 (2' HYDROXY 1,1' BIPHENYL 4 YL) 6 OXOTHIENO[2,3 B]PYRIDINE 5 CARBONITRILE; C 24; CINACIGUAT; CURCUMIN; ENZYME ACTIVATOR; EPICATECHIN; ESTROGEN; JTP 70902; METFORMIN; N ACETYL S NITROSOPENICILLAMINE; N [2 [3 (1 PIPERAZINYLMETHYL)IMIDAZO[2,1 B]THIAZOL 6 YL]PHENYL] 2 QUINOXALINECARBOXAMIDE; NITROPRUSSIDE SODIUM; PHENFORMIN; PHYTOESTROGEN; R 419; RESVERATROL; RIOCIGUAT; SRT 1460; SRT 2104; SRT 2183; TADALAFIL; TRAMETINIB; UDENAFIL; UNCLASSIFIED DRUG; UNINDEXED DRUG; VARDENAFIL; ZAPRINAST; BIOLOGICAL PRODUCT;

ACUTE DISEASE; ARTICLE; CHRONIC DISEASE; DEGENERATIVE DISEASE; DRUG MECHANISM; ENZYME ACTIVATION; HUMAN; MITOCHONDRIAL BIOGENESIS; MITOCHONDRION; NONHUMAN; OXIDATIVE STRESS; PHASE 3 CLINICAL TRIAL (TOPIC); PROTEIN EXPRESSION; CHEMICAL STRUCTURE; CHEMISTRY; DISEASES; DRUG EFFECTS; METABOLISM; ORGANELLE BIOGENESIS;

ACUTE DISEASE; BIOLOGICAL PRODUCTS; CHRONIC DISEASE; DISEASE; HUMANS; MITOCHONDRIA; MOLECULAR STRUCTURE; ORGANELLE BIOGENESIS;

EID: 85003550776     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/acs.jmedchem.6b00669     Document Type: Article

References (331)

1. Whitaker, R. M.; Corum, D.; Beeson, C. C.; Schnellmann, R. G. Mitochondrial Biogenesis as a Pharmacological Target: A New Approach to Acute and Chronic Diseases Annu. Rev. Pharmacol. Toxicol. 2016, 56, 229-249 10.1146/annurev-pharmtox-010715-103155
2. Nunnari, J.; Suomalainen, A. Mitochondria: In Sickness and in Health Cell 2012, 148 ( 6 ) 1145-1159 10.1016/j.cell.2012.02.035
3. Lane, R. K.; Hilsabeck, T.; Rea, S. L. The Role of Mitochondrial Dysfunction in Age-Related Diseases Biochim. Biophys. Acta, Bioenerg. 2015, 1847 ( 11 ) 1387-1400 10.1016/j.bbabio.2015.05.021
4. Hafizi Abu Bakar, M.; Kian Kai, C.; Wan Hassan, W. N.; Sarmidi, M. R.; Yaakob, H.; Zaman Huri, H. Mitochondrial Dysfunction as a Central Event for Mechanisms Underlying Insulin Resistance: The Roles of Long Chain Fatty Acids Diabetes/Metab. Res. Rev. 2015, 31 ( 5 ) 453-475 10.1002/dmrr.2601
5. Walters, J. W.; Amos, D.; Ray, K.; Santanam, N. Mitochondrial Redox Status as a Target for Cardiovascular Disease Curr. Opin. Pharmacol. 2016, 27, 50-55 10.1016/j.coph.2016.01.006
6. Bonawitz, N. D.; Clayton, D. A.; Shadel, G. S. Initiation and Beyond: Multiple Functions of the Human Mitochondrial Transcription Machinery Mol. Cell 2006, 24 ( 6 ) 813-825 10.1016/j.molcel.2006.11.024
7. Scarpulla, R. C. Transcriptional Paradigms in Mammalian Mitochondrial Biogenesis and Function Physiol. Rev. 2008, 88 ( 2 ) 611-638 10.1152/physrev.00025.2007
8. Copeland, W. C.; Longley, M. J. Mitochondrial Genome Maintenance in Health and Disease DNA Repair 2014, 19, 190-198 10.1016/j.dnarep.2014.03.010
9. Milenkovic, D.; Matic, S.; Kuhl, I.; Ruzzenente, B.; Freyer, C.; Jemt, E.; Park, C. B.; Falkenberg, M.; Larsson, N. G. TWINKLE Is an Essential Mitochondrial Helicase Required for Synthesis of Nascent D-Loop Strands and Complete mtDNA Replication Hum. Mol. Genet. 2013, 22 ( 10 ) 1983-1993 10.1093/hmg/ddt051
10. Villena, J. A. New Insights into PGC-1 Coactivators: Redefining Their Role in the Regulation of Mitochondrial Function and Beyond FEBS J. 2015, 282 ( 4 ) 647-672 10.1111/febs.13175
11. Valle, I.; Alvarez-Barrientos, A.; Arza, E.; Lamas, S.; Monsalve, M. PGC-1alpha Regulates the Mitochondrial Antioxidant Defense System in Vascular Endothelial Cells Cardiovasc. Res. 2005, 66 ( 3 ) 562-573 10.1016/j.cardiores.2005.01.026
12. Soriano, F. X.; Liesa, M.; Bach, D.; Chan, D. C.; Palacin, M.; Zorzano, A. Evidence for a Mitochondrial Regulatory Pathway Defined by Peroxisome Proliferator-Activated Receptor-Gamma Coactivator-1 Alpha, Estrogen-Related Receptor-Alpha, and Mitofusin 2 Diabetes 2006, 55 ( 6 ) 1783-1791 10.2337/db05-0509
13. Kotiadis, V. N.; Duchen, M. R.; Osellame, L. D. Mitochondrial Quality Control and Communications with the Nucleus Are Important in Maintaining Mitochondrial Function and Cell Health Biochim. Biophys. Acta, Gen. Subj. 2014, 1840 ( 4 ) 1254-1265 10.1016/j.bbagen.2013.10.041
14. Scarpulla, R. C. Metabolic Control of Mitochondrial Biogenesis through the PGC-1 Family Regulatory Network Biochim. Biophys. Acta, Mol. Cell Res. 2011, 1813 ( 7 ) 1269-1278 10.1016/j.bbamcr.2010.09.019
15. Pardo, R.; Enguix, N.; Lasheras, J.; Feliu, J. E.; Kralli, A.; Villena, J. A. Rosiglitazone-Induced Mitochondrial Biogenesis in White Adipose Tissue is Independent of Peroxisome Proliferator-Activated Receptor Gamma Coactivator-1alpha PLoS One 2011, 6 ( 11 ) e26989 10.1371/journal.pone.0026989
16. Peeters, A.; Shinde, A. B.; Dirkx, R.; Smet, J.; De Bock, K.; Espeel, M.; Vanhorebeek, I.; Vanlander, A.; Van Coster, R.; Carmeliet, P.; Fransen, M.; Van Veldhoven, P. P.; Baes, M. Mitochondria in Peroxisome-Deficient Hepatocytes Exhibit Impaired Respiration, Depleted DNA, and PGC-1alpha Independent Proliferation Biochim. Biophys. Acta, Mol. Cell Res. 2015, 1853 ( 2 ) 285-298 10.1016/j.bbamcr.2014.11.017
17. Rowe, G. C.; Patten, I. S.; Zsengeller, Z. K.; El-Khoury, R.; Okutsu, M.; Bampoh, S.; Koulisis, N.; Farrell, C.; Hirshman, M. F.; Yan, Z.; Goodyear, L. J.; Rustin, P.; Arany, Z. Disconnecting Mitochondrial Content from Respiratory Chain Capacity in PGC-1-Deficient Skeletal Muscle Cell Rep. 2013, 3 ( 5 ) 1449-1456 10.1016/j.celrep.2013.04.023
18. Wilson, L.; Yang, Q.; Szustakowski, J. D.; Gullicksen, P. S.; Halse, R. Pyruvate Induces Mitochondrial Biogenesis by a PGC-1 Alpha-Independent Mechanism Am. J. Physiol. Cell Physiol. 2007, 292 ( 5 ) C1599-C1605 10.1152/ajpcell.00428.2006
19. Rodgers, J. T.; Lerin, C.; Haas, W.; Gygi, S. P.; Spiegelman, B. M.; Puigserver, P. Nutrient Control of Glucose Homeostasis through a Complex of PGC-1alpha and SIRT1 Nature 2005, 434 ( 7029 ) 113-118 10.1038/nature03354
20. Teyssier, C.; Ma, H.; Emter, R.; Kralli, A.; Stallcup, M. R. Activation of Nuclear Receptor Coactivator PGC-1alpha by Arginine Methylation Genes Dev. 2005, 19 ( 12 ) 1466-1473 10.1101/gad.1295005
21. Puigserver, P.; Rhee, J.; Lin, J.; Wu, Z.; Yoon, J. C.; Zhang, C. Y.; Krauss, S.; Mootha, V. K.; Lowell, B. B.; Spiegelman, B. M. Cytokine Stimulation of Energy Expenditure through p38 MAP Kinase Activation of PPARgamma Coactivator-1 Mol. Cell 2001, 8 ( 5 ) 971-982 10.1016/S1097-2765(01)00390-2
22. Chang, J. S.; Huypens, P.; Zhang, Y.; Black, C.; Kralli, A.; Gettys, T. W. Regulation of NT-PGC-1alpha Subcellular Localization and Function by Protein Kinase A-Dependent Modulation of Nuclear Export by CRM1 J. Biol. Chem. 2010, 285 ( 23 ) 18039-18050 10.1074/jbc.M109.083121
23. Jager, S.; Handschin, C.; St-Pierre, J.; Spiegelman, B. M. AMP-Activated Protein Kinase (AMPK) Action in Skeletal Muscle via Direct Phosphorylation of PGC-1alpha Proc. Natl. Acad. Sci. U. S. A. 2007, 104 ( 29 ) 12017-12022 10.1073/pnas.0705070104
24. Ventura-Clapier, R.; Garnier, A.; Veksler, V. Transcriptional Control of Mitochondrial Biogenesis: The Central Role of PGC-1alpha Cardiovasc. Res. 2008, 79 ( 2 ) 208-217 10.1093/cvr/cvn098
25. Rosca, M. G.; Vazquez, E. J.; Kerner, J.; Parland, W.; Chandler, M. P.; Stanley, W.; Sabbah, H. N.; Hoppel, C. L. Cardiac Mitochondria in Heart Failure: Decrease in Respirasomes and Oxidative Phosphorylation Cardiovasc. Res. 2008, 80 ( 1 ) 30-39 10.1093/cvr/cvn184
26. Canevari, L.; Kuroda, S.; Bates, T. E.; Clark, J. B.; Siesjo, B. K. Activity of Mitochondrial Respiratory Chain Enzymes after Transient Focal Ischemia in the Rat J. Cereb. Blood Flow Metab. 1997, 17 ( 11 ) 1166-1169 10.1097/00004647-199711000-00005
27. Funk, J. A.; Schnellmann, R. G. Persistent Disruption of Mitochondrial Homeostasis after Acute Kidney Injury Am. J. Physiol. Renal Physiol. 2012, 302 ( 7 ) F853-864 10.1152/ajprenal.00035.2011
28. O’Brien, L. C.; Keeney, P. M.; Bennett, J. P., Jr. Differentiation of Human Neural Stem Cells into Motor Neurons Stimulates Mitochondrial Biogenesis and Decreases Glycolytic Flux Stem Cells Dev. 2015, 24 ( 17 ) 1984-1994 10.1089/scd.2015.0076
29. Fortini, P.; Ferretti, C.; Iorio, E.; Cagnin, M.; Garribba, L.; Pietraforte, D.; Falchi, M.; Pascucci, B.; Baccarini, S.; Morani, F.; Phadngam, S.; De Luca, G.; Isidoro, C.; Dogliotti, E. The Fine Tuning of Metabolism, Autophagy and Differentiation during In Vitro Myogenesis Cell Death Dis. 2016, 7, e2168 10.1038/cddis.2016.50
30. van der Windt, G. J.; Pearce, E. L. Metabolic Switching and Fuel Choice during T-Cell Differentiation and Memory Development Immunol. Rev. 2012, 249 ( 1 ) 27-42 10.1111/j.1600-065X.2012.01150.x
31. Granata, S.; Zaza, G.; Simone, S.; Villani, G.; Latorre, D.; Pontrelli, P.; Carella, M.; Schena, F. P.; Grandaliano, G.; Pertosa, G. Mitochondrial Dysregulation and Oxidative Stress in Patients with Chronic Kidney Disease BMC Genomics 2009, 10, 388 10.1186/1471-2164-10-388
32. Murray, A. J.; Cole, M. A.; Lygate, C. A.; Carr, C. A.; Stuckey, D. J.; Little, S. E.; Neubauer, S.; Clarke, K. Increased Mitochondrial Uncoupling Proteins, Respiratory Uncoupling and Decreased Efficiency in the Chronically Infarcted Rat Heart J. Mol. Cell. Cardiol. 2008, 44 ( 4 ) 694-700 10.1016/j.yjmcc.2008.01.008
33. Garnier, A.; Fortin, D.; Delomenie, C.; Momken, I.; Veksler, V.; Ventura-Clapier, R. Depressed Mitochondrial Transcription Factors and Oxidative Capacity in Rat Failing Cardiac and Skeletal Muscles J. Physiol. 2003, 551 ( 2 ) 491-501 10.1113/jphysiol.2003.045104
34. Sebastiani, M.; Giordano, C.; Nediani, C.; Travaglini, C.; Borchi, E.; Zani, M.; Feccia, M.; Mancini, M.; Petrozza, V.; Cossarizza, A.; Gallo, P.; Taylor, R. W.; d’Amati, G. Induction of Mitochondrial Biogenesis Is a Maladaptive Mechanism in Mitochondrial Cardiomyopathies J. Am. Coll. Cardiol. 2007, 50 ( 14 ) 1362-1369 10.1016/j.jacc.2007.06.035
35. Russell, L. K.; Mansfield, C. M.; Lehman, J. J.; Kovacs, A.; Courtois, M.; Saffitz, J. E.; Medeiros, D. M.; Valencik, M. L.; McDonald, J. A.; Kelly, D. P. Cardiac-Specific Induction of the Transcriptional Coactivator Peroxisome Proliferator-Activated Receptor Gamma Coactivator-1alpha Promotes Mitochondrial Biogenesis and Reversible Cardiomyopathy in a Developmental Stage-Dependent Manner Circ. Res. 2004, 94 ( 4 ) 525-533 10.1161/01.RES.0000117088.36577.EB
36. Gamboa, J. L.; Billings, F.T.t.; Bojanowski, M. T.; Gilliam, L. A.; Yu, C.; Roshanravan, B.; Roberts, L. J., 2nd; Himmelfarb, J.; Ikizler, T. A.; Brown, N. J. Mitochondrial Dysfunction and Oxidative Stress in Patients with Chronic Kidney Disease Physiol. Rep. 2016, 4 ( 9 ) e12780 10.14814/phy2.12780
37. Coughlan, M. T.; Higgins, G. C.; Nguyen, T. V.; Penfold, S. A.; Thallas-Bonke, V.; Tan, S. M.; Ramm, G.; Van Bergen, N. J.; Henstridge, D. C.; Sourris, K. C.; Harcourt, B. E.; Trounce, I. A.; Robb, P. M.; Laskowski, A.; McGee, S. L.; Genders, A. J.; Walder, K.; Drew, B. G.; Gregorevic, P.; Qian, H.; Thomas, M. C.; Jerums, G.; Macisaac, R. J.; Skene, A.; Power, D. A.; Ekinci, E. I.; Wijeyeratne, X. W.; Gallo, L. A.; Herman-Edelstein, M.; Ryan, M. T.; Cooper, M. E.; Thorburn, D. R.; Forbes, J. M. Deficiency in Apoptosis-Inducing Factor Recapitulates Chronic Kidney Disease via Aberrant Mitochondrial Homeostasis Diabetes 2016, 65 ( 4 ) 1085-1098 10.2337/db15-0864
38. Blaak, E. E.; van Aggel-Leijssen, D. P.; Wagenmakers, A. J.; Saris, W. H.; van Baak, M. A. Impaired Oxidation of Plasma-Derived Fatty Acids in Type 2 Diabetic Subjects during Moderate-Intensity Exercise Diabetes 2000, 49 ( 12 ) 2102-2107 10.2337/diabetes.49.12.2102
39. Joseph, J. W.; Koshkin, V.; Saleh, M. C.; Sivitz, W. I.; Zhang, C. Y.; Lowell, B. B.; Chan, C. B.; Wheeler, M. B. Free Fatty Acid-Induced Beta-Cell Defects Are Dependent on Uncoupling Protein 2 Expression J. Biol. Chem. 2004, 279 ( 49 ) 51049-51056 10.1074/jbc.M409189200
40. Zhang, C. Y.; Baffy, G.; Perret, P.; Krauss, S.; Peroni, O.; Grujic, D.; Hagen, T.; Vidal-Puig, A. J.; Boss, O.; Kim, Y. B.; Zheng, X. X.; Wheeler, M. B.; Shulman, G. I.; Chan, C. B.; Lowell, B. B. Uncoupling Protein-2 Negatively Regulates Insulin Secretion and Is a Major Link between Obesity, Beta Cell Dysfunction, and Type 2 Diabetes Cell 2001, 105 ( 6 ) 745-755 10.1016/S0092-8674(01)00378-6
41. Van der Schueren, B.; Vangoitsenhoven, R.; Geeraert, B.; De Keyzer, D.; Hulsmans, M.; Lannoo, M.; Huber, H. J.; Mathieu, C.; Holvoet, P. Low Cytochrome Oxidase 4I1 Links Mitochondrial Dysfunction to Obesity and Type 2 Diabetes in Humans and Mice Int. J. Obes. 2015, 39 ( 8 ) 1254-1263 10.1038/ijo.2015.58
42. Ling, C.; Poulsen, P.; Simonsson, S.; Ronn, T.; Holmkvist, J.; Almgren, P.; Hagert, P.; Nilsson, E.; Mabey, A. G.; Nilsson, P.; Vaag, A.; Groop, L. Genetic and Epigenetic Factors Are Associated with Expression of Respiratory Chain Component NDUFB6 in Human Skeletal Muscle J. Clin. Invest. 2007, 117 ( 11 ) 3427-3435 10.1172/JCI30938
43. Ronn, T.; Poulsen, P.; Hansson, O.; Holmkvist, J.; Almgren, P.; Nilsson, P.; Tuomi, T.; Isomaa, B.; Groop, L.; Vaag, A.; Ling, C. Age Influences DNA Methylation and Gene Expression of COX7A1 in Human Skeletal Muscle Diabetologia 2008, 51 ( 7 ) 1159-1168 10.1007/s00125-008-1018-8
44. Zheng, L. D.; Linarelli, L. E.; Brooke, J.; Smith, C.; Wall, S. S.; Greenawald, M. H.; Seidel, R. W.; Estabrooks, P. A.; Almeida, F. A.; Cheng, Z. Mitochondrial Epigenetic Changes Link to Increased Diabetes Risk and Early-Stage Prediabetes Indicator Oxid. Med. Cell. Longevity 2016, 10.1155/2016/5290638
45. Ling, C.; Del Guerra, S.; Lupi, R.; Ronn, T.; Granhall, C.; Luthman, H.; Masiello, P.; Marchetti, P.; Groop, L.; Del Prato, S. Epigenetic Regulation of PPARGC1A in Human Type 2 Diabetic Islets and Effect on Insulin Secretion Diabetologia 2008, 51 ( 4 ) 615-622 10.1007/s00125-007-0916-5
46. Choi, Y. S.; Kim, S.; Pak, Y. K. Mitochondrial Transcription Factor A (mtTFA) and Diabetes Diabetes Res. Clin. Pract. 2001, 54 ( Suppl 2 ) S3-9 10.1016/S0168-8227(01)00330-8
47. Zuo, L.; Motherwell, M. S. The Impact of Reactive Oxygen Species and Genetic Mitochondrial Mutations in Parkinson’s Disease Gene 2013, 532 ( 1 ) 18-23 10.1016/j.gene.2013.07.085
48. Palacino, J. J.; Sagi, D.; Goldberg, M. S.; Krauss, S.; Motz, C.; Wacker, M.; Klose, J.; Shen, J. Mitochondrial Dysfunction and Oxidative Damage in Parkin-Deficient Mice J. Biol. Chem. 2004, 279 ( 18 ) 18614-18622 10.1074/jbc.M401135200
49. Liu, W.; Vives-Bauza, C.; Acin-Perez, R.; Yamamoto, A.; Tan, Y.; Li, Y.; Magrane, J.; Stavarache, M. A.; Shaffer, S.; Chang, S.; Kaplitt, M. G.; Huang, X. Y.; Beal, M. F.; Manfredi, G.; Li, C. PINK1 Defect Causes Mitochondrial Dysfunction, Proteasomal Deficit and Alpha-Synuclein Aggregation in Cell Culture Models of Parkinson’s Disease PLoS One 2009, 4 ( 2 ) e4597 10.1371/journal.pone.0004597
50. Gautier, C. A.; Kitada, T.; Shen, J. Loss of PINK1 Causes Mitochondrial Functional Defects and Increased Sensitivity to Oxidative Stress Proc. Natl. Acad. Sci. U. S. A. 2008, 105 ( 32 ) 11364-11369 10.1073/pnas.0802076105
51. Krebiehl, G.; Ruckerbauer, S.; Burbulla, L. F.; Kieper, N.; Maurer, B.; Waak, J.; Wolburg, H.; Gizatullina, Z.; Gellerich, F. N.; Woitalla, D.; Riess, O.; Kahle, P. J.; Proikas-Cezanne, T.; Kruger, R. Reduced Basal Autophagy and Impaired Mitochondrial Dynamics due to Loss of Parkinson’s Disease-Associated Protein DJ-1 PLoS One 2010, 5 ( 2 ) e9367 10.1371/journal.pone.0009367
52. Gu, G.; Reyes, P. E.; Golden, G. T.; Woltjer, R. L.; Hulette, C.; Montine, T. J.; Zhang, J. Mitochondrial DNA Deletions/Rearrangements in Parkinson Disease and Related Neurodegenerative Disorders J. Neuropathol. Exp. Neurol. 2002, 61 ( 7 ) 634-639 10.1093/jnen/61.7.634
53. Ikebe, S.; Tanaka, M.; Ozawa, T. Point Mutations of Mitochondrial Genome in Parkinson’s Disease Mol. Brain Res. 1995, 28 ( 2 ) 281-295 10.1016/0169-328X(94)00209-W
54. Simon, D. K.; Lin, M. T.; Zheng, L.; Liu, G. J.; Ahn, C. H.; Kim, L. M.; Mauck, W. M.; Twu, F.; Beal, M. F.; Johns, D. R. Somatic Mitochondrial DNA Mutations in Cortex and Substantia Nigra in Aging and Parkinson’s Disease Neurobiol. Aging 2004, 25 ( 1 ) 71-81 10.1016/S0197-4580(03)00037-X
55. Simon, D. K.; Pulst, S. M.; Sutton, J. P.; Browne, S. E.; Beal, M. F.; Johns, D. R. Familial Multisystem Degeneration with Parkinsonism Associated with the 11778 Mitochondrial DNA Mutation Neurology 1999, 53 ( 8 ) 1787-1793 10.1212/WNL.53.8.1787
56. Ekstrand, M. I.; Terzioglu, M.; Galter, D.; Zhu, S.; Hofstetter, C.; Lindqvist, E.; Thams, S.; Bergstrand, A.; Hansson, F. S.; Trifunovic, A.; Hoffer, B.; Cullheim, S.; Mohammed, A. H.; Olson, L.; Larsson, N. G. Progressive Parkinsonism in Mice with Respiratory-Chain-Deficient Dopamine Neurons Proc. Natl. Acad. Sci. U. S. A. 2007, 104 ( 4 ) 1325-1330 10.1073/pnas.0605208103
57. Burbulla, L. F.; Schelling, C.; Kato, H.; Rapaport, D.; Woitalla, D.; Schiesling, C.; Schulte, C.; Sharma, M.; Illig, T.; Bauer, P.; Jung, S.; Nordheim, A.; Schols, L.; Riess, O.; Kruger, R. Dissecting the Role of the Mitochondrial Chaperone Mortalin in Parkinson’s Disease: Functional Impact of Disease-Related Variants on Mitochondrial Homeostasis Hum. Mol. Genet. 2010, 19 ( 22 ) 4437-4452 10.1093/hmg/ddq370
58. Devi, L.; Raghavendran, V.; Prabhu, B. M.; Avadhani, N. G.; Anandatheerthavarada, H. K. Mitochondrial Import and Accumulation of Alpha-Synuclein Impair Complex I in Human Dopaminergic Neuronal Cultures and Parkinson Disease Brain J. Biol. Chem. 2008, 283 ( 14 ) 9089-9100 10.1074/jbc.M710012200
59. Cui, L.; Jeong, H.; Borovecki, F.; Parkhurst, C. N.; Tanese, N.; Krainc, D. Transcriptional Repression of PGC-1alpha by Mutant Huntingtin Leads to Mitochondrial Dysfunction and Neurodegeneration Cell 2006, 127 ( 1 ) 59-69 10.1016/j.cell.2006.09.015
60. Chaturvedi, R. K.; Hennessey, T.; Johri, A.; Tiwari, S. K.; Mishra, D.; Agarwal, S.; Kim, Y. S.; Beal, M. F. Transducer of Regulated CREB-Binding Proteins (TORCs) Transcription and Function Is Impaired in Huntington’s Disease Hum. Mol. Genet. 2012, 21 ( 15 ) 3474-3488 10.1093/hmg/dds178
61. Panov, A. V.; Gutekunst, C. A.; Leavitt, B. R.; Hayden, M. R.; Burke, J. R.; Strittmatter, W. J.; Greenamyre, J. T. Early Mitochondrial Calcium Defects in Huntington’s Disease Are a Direct Effect of Polyglutamines Nat. Neurosci. 2002, 5 ( 8 ) 731-736 10.1038/nn884
62. Gu, M.; Gash, M. T.; Mann, V. M.; Javoy-Agid, F.; Cooper, J. M.; Schapira, A. H. Mitochondrial Defect in Huntington’s Disease Caudate Nucleus Ann. Neurol. 1996, 39 ( 3 ) 385-389 10.1002/ana.410390317
63. Milakovic, T.; Johnson, G. V. Mitochondrial Respiration and ATP Production are Significantly Impaired in Striatal Cells Expressing Mutant Huntingtin J. Biol. Chem. 2005, 280 ( 35 ) 30773-30782 10.1074/jbc.M504749200
64. Bayram-Weston, Z.; Torres, E. M.; Jones, L.; Dunnett, S. B.; Brooks, S. P. Light and Electron Microscopic Characterization of the Evolution of Cellular Pathology in the Hdh(CAG)150 Huntington’s Disease Knock-In Mouse Brain Res. Bull. 2012, 88 ( 2-3 ) 189-198 10.1016/j.brainresbull.2011.03.014
65. Squitieri, F.; Falleni, A.; Cannella, M.; Orobello, S.; Fulceri, F.; Lenzi, P.; Fornai, F. Abnormal Morphology of Peripheral Cell Tissues from Patients with Huntington Disease J. Neural Transm. 2010, 117 ( 1 ) 77-83 10.1007/s00702-009-0328-4
66. Rice, A. C.; Keeney, P. M.; Algarzae, N. K.; Ladd, A. C.; Thomas, R. R.; Bennett, J. P., Jr. Mitochondrial DNA Copy Numbers in Pyramidal Neurons Are Decreased and Mitochondrial Biogenesis Transcriptome Signaling Is Disrupted in Alzheimer’s Disease Hippocampi J. Alzheimers Dis. 2014, 40 ( 2 ) 319-330 10.3233/JAD-131715
67. Ojaimi, J.; Masters, C. L.; McLean, C.; Opeskin, K.; McKelvie, P.; Byrne, E. Irregular Distribution of Cytochrome C Oxidase Protein Subunits in Aging and Alzheimer’s Disease Ann. Neurol. 1999, 46 ( 4 ) 656-660 10.1002/1531-8249(199910)46:4<656::AID-ANA16>3.0.CO;2-Q
68. Wang, J.; Xiong, S.; Xie, C.; Markesbery, W. R.; Lovell, M. A. Increased Oxidative Damage in Nuclear and Mitochondrial DNA in Alzheimer’s Disease J. Neurochem. 2005, 93 ( 4 ) 953-962 10.1111/j.1471-4159.2005.03053.x
69. Moreira, P. I.; Siedlak, S. L.; Wang, X.; Santos, M. S.; Oliveira, C. R.; Tabaton, M.; Nunomura, A.; Szweda, L. I.; Aliev, G.; Smith, M. A.; Zhu, X.; Perry, G. Autophagocytosis of Mitochondria Is Prominent in Alzheimer Disease J. Neuropathol. Exp. Neurol. 2007, 66 ( 6 ) 525-532 10.1097/01.jnen.0000240476.73532.b0
70. Wang, X.; Su, B.; Fujioka, H.; Zhu, X. Dynamin-Like Protein 1 Reduction Underlies Mitochondrial Morphology and Distribution Abnormalities in Fibroblasts from Sporadic Alzheimer’s Disease Patients Am. J. Pathol. 2008, 173 ( 2 ) 470-482 10.2353/ajpath.2008.071208
71. Funk, J. A.; Schnellmann, R. G. Accelerated Recovery of Renal Mitochondrial and Tubule Homeostasis with SIRT1/PGC-1alpha Activation Following Ischemia-Reperfusion Injury Toxicol. Appl. Pharmacol. 2013, 273 ( 2 ) 345-354 10.1016/j.taap.2013.09.026
72. Takaoka, M. Resveratrol, a New Phenolic Compound, from Veratrum Grandiflorum Nippon Kagaku Kaishi 1939, 60, 1090-1100 10.1246/nikkashi1921.60.1090
73. Lagouge, M.; Argmann, C.; Gerhart-Hines, Z.; Meziane, H.; Lerin, C.; Daussin, F.; Messadeq, N.; Milne, J.; Lambert, P.; Elliott, P.; Geny, B.; Laakso, M.; Puigserver, P.; Auwerx, J. Resveratrol Improves Mitochondrial Function and Protects against Metabolic Disease by Activating SIRT1 and PGC-1alpha Cell 2006, 127 ( 6 ) 1109-1122 10.1016/j.cell.2006.11.013
74. Gledhill, J. R.; Montgomery, M. G.; Leslie, A. G.; Walker, J. E. Mechanism of Inhibition of Bovine F1-ATPase by Resveratrol and Related Polyphenols Proc. Natl. Acad. Sci. U. S. A. 2007, 104 ( 34 ) 13632-13637 10.1073/pnas.0706290104
75. Gueguen, N.; Desquiret-Dumas, V.; Leman, G.; Chupin, S.; Baron, S.; Nivet-Antoine, V.; Vessieres, E.; Ayer, A.; Henrion, D.; Lenaers, G.; Reynier, P.; Procaccio, V. Resveratrol Directly Binds to Mitochondrial Complex I and Increases Oxidative Stress in Brain Mitochondria of Aged Mice PLoS One 2015, 10 ( 12 ) e0144290 10.1371/journal.pone.0144290
76. Takizawa, Y.; Nakata, R.; Fukuhara, K.; Yamashita, H.; Kubodera, H.; Inoue, H. The 4’-Hydroxyl Group of Resveratrol Is Functionally Important for Direct Activation of PPARalpha PLoS One 2015, 10 ( 3 ) e0120865 10.1371/journal.pone.0120865
77. Calleri, E.; Pochetti, G.; Dossou, K. S.; Laghezza, A.; Montanari, R.; Capelli, D.; Prada, E.; Loiodice, F.; Massolini, G.; Bernier, M.; Moaddel, R. Resveratrol and Its Metabolites Bind to PPARs ChemBioChem 2014, 15 ( 8 ) 1154-1160 10.1002/cbic.201300754
78. Joshi, M. S.; Williams, D.; Horlock, D.; Samarasinghe, T.; Andrews, K. L.; Jefferis, A. M.; Berger, P. J.; Chin-Dusting, J. P.; Kaye, D. M. Role of Mitochondrial Dysfunction in Hyperglycaemia-Induced Coronary Microvascular Dysfunction: Protective Role of Resveratrol Diabetes Vasc. Dis. Res. 2015, 12 ( 3 ) 208-216 10.1177/1479164114565629
79. Li, J.; Feng, L.; Xing, Y.; Wang, Y.; Du, L.; Xu, C.; Cao, J.; Wang, Q.; Fan, S.; Liu, Q.; Fan, F. Radioprotective and Antioxidant Effect of Resveratrol in Hippocampus by Activating Sirt1 Int. J. Mol. Sci. 2014, 15 ( 4 ) 5928-5939 10.3390/ijms15045928
80. Porquet, D.; Grinan-Ferre, C.; Ferrer, I.; Camins, A.; Sanfeliu, C.; Del Valle, J.; Pallas, M. Neuroprotective Role of trans-Resveratrol in a Murine Model of Familial Alzheimer’s Disease J. Alzheimers Dis. 2014, 42 ( 4 ) 1209-1220 10.3233/JAD-140444
81. Ferretta, A.; Gaballo, A.; Tanzarella, P.; Piccoli, C.; Capitanio, N.; Nico, B.; Annese, T.; Di Paola, M.; Dell’aquila, C.; De Mari, M.; Ferranini, E.; Bonifati, V.; Pacelli, C.; Cocco, T. Effect of Resveratrol on Mitochondrial Function: Implications in Parkin-Associated Familiar Parkinson’s Disease Biochim. Biophys. Acta, Mol. Basis Dis. 2014, 1842 ( 7 ) 902-915 10.1016/j.bbadis.2014.02.010
82. Solans, A.; Zambrano, A.; Rodriguez, M.; Barrientos, A. Cytotoxicity of a Mutant Huntingtin Fragment in Yeast Involves Early Alterations in Mitochondrial OXPHOS Complexes II and III Hum. Mol. Genet. 2006, 15 ( 20 ) 3063-3081 10.1093/hmg/ddl248
83. Mathieu, L.; Costa, A. L.; Le Bachelier, C.; Slama, A.; Lebre, A. S.; Taylor, R. W.; Bastin, J.; Djouadi, F. Resveratrol Attenuates Oxidative Stress in Mitochondrial Complex I Deficiency: Involvement of SIRT3 Free Radical Biol. Med. 2016, 96, 190-198 10.1016/j.freeradbiomed.2016.04.027
84. Brasnyo, P.; Molnar, G. A.; Mohas, M.; Marko, L.; Laczy, B.; Cseh, J.; Mikolas, E.; Szijarto, I. A.; Merei, A.; Halmai, R.; Meszaros, L. G.; Sumegi, B.; Wittmann, I. Resveratrol Improves Insulin Sensitivity, Reduces Oxidative Stress and Activates the Akt Pathway in Type 2 Diabetic Patients Br. J. Nutr. 2011, 106 ( 3 ) 383-389 10.1017/S0007114511000316
85. Timmers, S.; Konings, E.; Bilet, L.; Houtkooper, R. H.; van de Weijer, T.; Goossens, G. H.; Hoeks, J.; van der Krieken, S.; Ryu, D.; Kersten, S.; Moonen-Kornips, E.; Hesselink, M. K.; Kunz, I.; Schrauwen-Hinderling, V. B.; Blaak, E. E.; Auwerx, J.; Schrauwen, P. Calorie Restriction-Like Effects of 30 days of Resveratrol Supplementation on Energy Metabolism and Metabolic Profile in Obese Humans Cell Metab. 2011, 14 ( 5 ) 612-622 10.1016/j.cmet.2011.10.002
86. Wong, R. H.; Howe, P. R.; Buckley, J. D.; Coates, A. M.; Kunz, I.; Berry, N. M. Acute Resveratrol Supplementation Improves Flow-Mediated Dilatation in Overweight/Obese Individuals with Mildly Elevated Blood Pressure Nutr., Metab. Cardiovasc. Dis. 2011, 21 ( 11 ) 851-856 10.1016/j.numecd.2010.03.003
87. Bhatt, J. K.; Thomas, S.; Nanjan, M. J. Resveratrol Supplementation Improves Glycemic Control in Type 2 Diabetes Mellitus Nutr. Res. (N. Y., NY, U. S.) 2012, 32 ( 7 ) 537-541 10.1016/j.nutres.2012.06.003
88. Crandall, J. P.; Oram, V.; Trandafirescu, G.; Reid, M.; Kishore, P.; Hawkins, M.; Cohen, H. W.; Barzilai, N. Pilot Study of Resveratrol in Older Adults with Impaired Glucose Tolerance J. Gerontol., Ser. A 2012, 67 ( 12 ) 1307-1312 10.1093/gerona/glr235
89. De Groote, D.; Van Belleghem, K.; Deviere, J.; Van Brussel, W.; Mukaneza, A.; Amininejad, L. Effect of the Intake of Resveratrol, Resveratrol Phosphate, and Catechin-Rich Grape Seed Extract on Markers of Oxidative Stress and Gene Expression in Adult Obese Subjects Ann. Nutr. Metab. 2012, 61 ( 1 ) 15-24 10.1159/000338634
90. Poulsen, M. M.; Vestergaard, P. F.; Clasen, B. F.; Radko, Y.; Christensen, L. P.; Stodkilde-Jorgensen, H.; Moller, N.; Jessen, N.; Pedersen, S. B.; Jorgensen, J. O. High-Dose Resveratrol Supplementation in Obese Men: An Investigator-Initiated, Randomized, Placebo-Controlled Clinical Trial of Substrate Metabolism, Insulin Sensitivity, and Body Composition Diabetes 2013, 62 ( 4 ) 1186-1195 10.2337/db12-0975
91. Yoshino, J.; Conte, C.; Fontana, L.; Mittendorfer, B.; Imai, S.; Schechtman, K. B.; Gu, C.; Kunz, I.; Rossi Fanelli, F.; Patterson, B. W.; Klein, S. Resveratrol Supplementation Does Not Improve Metabolic Function in Nonobese Women with Normal Glucose Tolerance Cell Metab. 2012, 16 ( 5 ) 658-664 10.1016/j.cmet.2012.09.015
92. Freudenberg, K.; Cox, R. F. B.; Braun, E. The Catechin of the Cacao Bean J. Am. Chem. Soc. 1932, 54 ( 5 ) 1913-1917 10.1021/ja01344a026
93. Moreno-Ulloa, A.; Cid, A.; Rubio-Gayosso, I.; Ceballos, G.; Villarreal, F.; Ramirez-Sanchez, I. Effects of (−)-Epicatechin and Derivatives on Nitric Oxide Mediated Induction of Mitochondrial Proteins Bioorg. Med. Chem. Lett. 2013, 23 ( 15 ) 4441-4446 10.1016/j.bmcl.2013.05.079
94. Nichols, M.; Zhang, J.; Polster, B. M.; Elustondo, P. A.; Thirumaran, A.; Pavlov, E. V.; Robertson, G. S. Synergistic Neuroprotection by Epicatechin and Quercetin: Activation of Convergent Mitochondrial Signaling Pathways Neuroscience 2015, 308, 75-94 10.1016/j.neuroscience.2015.09.012
95. Panneerselvam, M.; Ali, S. S.; Finley, J. C.; Kellerhals, S. E.; Migita, M. Y.; Head, B. P.; Patel, P. M.; Roth, D. M.; Patel, H. H. Epicatechin Regulation of Mitochondrial Structure and Function Is Opioid Receptor Dependent Mol. Nutr. Food Res. 2013, 57 ( 6 ) 1007-1014 10.1002/mnfr.201300026
96. Bondarovich, H. A.; Giammarino, A. S.; Renner, J. A.; Shephard, F. W.; Shingler, A. J.; Gianturco, M. A. Volatiles in Tea: Some Aspects of the Chemistry of Tea. A Contribution to the Knowledge of the Volatile Constituents J. Agric. Food Chem. 1967, 15 ( 1 ) 36-47 10.1021/jf60149a011
97. Valenti, D.; De Rasmo, D.; Signorile, A.; Rossi, L.; de Bari, L.; Scala, I.; Granese, B.; Papa, S.; Vacca, R. A. Epigallocatechin-3-Gallate Prevents Oxidative Phosphorylation Deficit and Promotes Mitochondrial Biogenesis in Human Cells from Subjects with Down’s Syndrome Biochim. Biophys. Acta, Mol. Basis Dis. 2013, 1832 ( 4 ) 542-552 10.1016/j.bbadis.2012.12.011
98. Kurita, I.; Kim, J. H.; Auger, C.; Kinoshita, Y.; Miyase, T.; Ito, T.; Schini-Kerth, V. B. Hydroxylation of (−)-Epigallocatechin-3-O-Gallate at 3, but Not 4’’, Is Essential for the PI3-Kinase/Akt-Dependent Phosphorylation of Endothelial NO Synthase in Endothelial Cells and Relaxation of Coronary Artery Rings Food Funct. 2013, 4 ( 2 ) 249-257 10.1039/C2FO30087G
99. Ramirez-Sanchez, I.; Rodriguez, A.; Moreno-Ulloa, A.; Ceballos, G.; Villarreal, F. (−)-Epicatechin-Induced Recovery of Mitochondria from Simulated Diabetes: Potential Role of Endothelial Nitric Oxide Synthase Diabetes Vasc. Dis. Res. 2016, 13 ( 3 ) 201-210 10.1177/1479164115620982
100. Yamazaki, K. G.; Andreyev, A. Y.; Ortiz-Vilchis, P.; Petrosyan, S.; Divakaruni, A. S.; Wiley, S. E.; De La Fuente, C.; Perkins, G.; Ceballos, G.; Villarreal, F.; Murphy, A. N. Intravenous (−)-Epicatechin Reduces Myocardial Ischemic Injury by Protecting Mitochondrial Function Int. J. Cardiol. 2014, 175 ( 2 ) 297-306 10.1016/j.ijcard.2014.05.009
101. Moreno-Ulloa, A.; Nogueira, L.; Rodriguez, A.; Barboza, J.; Hogan, M. C.; Ceballos, G.; Villarreal, F.; Ramirez-Sanchez, I. Recovery of Indicators of Mitochondrial Biogenesis, Oxidative Stress, and Aging With (−)-Epicatechin in Senile Mice J. Gerontol., Ser. A 2015, 70 ( 11 ) 1370-1378 10.1093/gerona/glu131
102. Taub, P. R.; Ramirez-Sanchez, I.; Ciaraldi, T. P.; Perkins, G.; Murphy, A. N.; Naviaux, R.; Hogan, M.; Maisel, A. S.; Henry, R. R.; Ceballos, G.; Villarreal, F. Alterations in Skeletal Muscle Indicators of Mitochondrial Structure and Biogenesis in Patients with Type 2 Diabetes and Heart Failure: Effects of Epicatechin Rich Cocoa Clin. Transl. Sci. 2012, 5 ( 1 ) 43-47 10.1111/j.1752-8062.2011.00357.x
103. Gupta, S. C.; Patchva, S.; Koh, W.; Aggarwal, B. B. Discovery of Curcumin, a Component of Golden Spice, and Its Miraculous Biological Activities Clin. Exp. Pharmacol. Physiol. 2012, 39 ( 3 ) 283-299 10.1111/j.1440-1681.2011.05648.x
104. Jeong, G. S.; Oh, G. S.; Pae, H. O.; Jeong, S. O.; Kim, Y. C.; Shin, M. K.; Seo, B. Y.; Han, S. Y.; Lee, H. S.; Jeong, J. G.; Koh, J. S.; Chung, H. T. Comparative Effects of Curcuminoids on Endothelial Heme Oxygenase-1 Expression: ortho-Methoxy Groups Are Essential to Enhance Heme Oxygenase Activity and Protection Exp. Mol. Med. 2006, 38 ( 4 ) 393-400 10.1038/emm.2006.46
105. Negrette-Guzman, M.; Garcia-Nino, W. R.; Tapia, E.; Zazueta, C.; Huerta-Yepez, S.; Leon-Contreras, J. C.; Hernandez-Pando, R.; Aparicio-Trejo, O. E.; Madero, M.; Pedraza-Chaverri, J. Curcumin Attenuates Gentamicin-Induced Kidney Mitochondrial Alterations: Possible Role of a Mitochondrial Biogenesis Mechanism Evid. Based Complement. Alternat. Med. 2015, 2015, 1 10.1155/2015/917435
106. Ray Hamidie, R. D.; Yamada, T.; Ishizawa, R.; Saito, Y.; Masuda, K. Curcumin Treatment Enhances the Effect of Exercise on Mitochondrial Biogenesis in Skeletal Muscle by Increasing cAMP Levels Metab., Clin. Exp. 2015, 64 ( 10 ) 1334-1347 10.1016/j.metabol.2015.07.010
107. Minassi, A.; Sanchez-Duffhues, G.; Collado, J. A.; Munoz, E.; Appendino, G. Dissecting the Pharmacophore of Curcumin. Which Structural Element is Critical for Which Action? J. Nat. Prod. 2013, 76 ( 6 ) 1105-1112 10.1021/np400148e
108. Kuo, J. J.; Chang, H. H.; Tsai, T. H.; Lee, T. Y. Curcumin Ameliorates Mitochondrial Dysfunction Associated with Inhibition of Gluconeogenesis in Free Fatty Acid-Mediated Hepatic Lipoapoptosis Int. J. Mol. Med. 2012, 30 ( 3 ) 643-649 10.3892/ijmm.2012.1020
109. Wang, S.; Wang, X.; Ye, Z.; Xu, C.; Zhang, M.; Ruan, B.; Wei, M.; Jiang, Y.; Zhang, Y.; Wang, L.; Lei, X.; Lu, Z. Curcumin Promotes Browning of White Adipose Tissue in a Norepinephrine-Dependent Way Biochem. Biophys. Res. Commun. 2015, 466 ( 2 ) 247-253 10.1016/j.bbrc.2015.09.018
110. van der Merwe, C.; van Dyk, H. C.; Engelbrecht, L.; van der Westhuizen, F. H.; Kinnear, C.; Loos, B.; Bardien, S. Curcumin Rescues a PINK1 Knock Down SH-SY5Y Cellular Model of Parkinson’s Disease from Mitochondrial Dysfunction and Cell Death Mol. Neurobiol. 2016, 10.1007/s12035-016-9843-0
111. Liu, L.; Zhang, W.; Wang, L.; Li, Y.; Tan, B.; Lu, X.; Deng, Y.; Zhang, Y.; Guo, X.; Mu, J.; Yu, G. Curcumin Prevents Cerebral Ischemia Reperfusion Injury via Increase of Mitochondrial Biogenesis Neurochem. Res. 2014, 39 ( 7 ) 1322-1331 10.1007/s11064-014-1315-1
112. Kuo, J. J.; Chang, H. H.; Tsai, T. H.; Lee, T. Y. Positive Effect of Curcumin on Inflammation and Mitochondrial Dysfunction in Obese Mice with Liver Steatosis Int. J. Mol. Med. 2012, 30 ( 3 ) 673-679 10.3892/ijmm.2012.1049
113. Walter, E. D. Genistin (an Isoflavone Glucoside) and Its Aglucone, Genistein, from Soybeans J. Am. Chem. Soc. 1941, 63 ( 12 ) 3273-3276 10.1021/ja01857a013
114. Bickoff, E. M.; Livingston, A. L.; Hendrickson, A. P.; Booth, A. N. Forage Estrogens, Relative Potencies of Several Estrogenlike Compounds Found in Forages J. Agric. Food Chem. 1962, 10 ( 5 ) 410-412 10.1021/jf60123a018
115. Hauge, J. G. Glucose Dehydrogenase of Bacterium Anitratum: An Enzyme with a Novel Prosthetic Group J. Biol. Chem. 1964, 239, 3630-3639
116. Bickoff, E. M.; Booth, A. N.; Lyman, R. L.; Livingston, A. L.; Thompson, C. R.; Deeds, F. Coumestrol, a New Estrogen Isolated from Forage Crops Science 1957, 126 ( 3280 ) 969-970 10.1126/science.126.3280.969-a
117. Marrian, G. F.; Haslewood, G. A. Equol, a New Inactive Phenol Isolated from the Ketohydroxyoestrin Fraction of Mares’ Urine Biochem. J. 1932, 26 ( 4 ) 1227-1232 10.1042/bj0261227
118. Tissier, R.; Waintraub, X.; Couvreur, N.; Gervais, M.; Bruneval, P.; Mandet, C.; Zini, R.; Enriquez, B.; Berdeaux, A.; Ghaleh, B. Pharmacological Postconditioning with the Phytoestrogen Genistein J. Mol. Cell. Cardiol. 2007, 42 ( 1 ) 79-87 10.1016/j.yjmcc.2006.10.007
119. Nadal-Serrano, M.; Pons, D. G.; Sastre-Serra, J.; Blanquer-Rossello Mdel, M.; Roca, P.; Oliver, J. Genistein Modulates Oxidative Stress in Breast Cancer Cell Lines According to ERalpha/ERbeta Ratio: Effects on Mitochondrial Functionality, Sirtuins, Uncoupling Protein 2 and Antioxidant Enzymes Int. J. Biochem. Cell Biol. 2013, 45 ( 9 ) 2045-2051 10.1016/j.biocel.2013.07.002
120. Rasbach, K. A.; Schnellmann, R. G. Isoflavones Promote Mitochondrial Biogenesis J. Pharmacol. Exp. Ther. 2008, 325 ( 2 ) 536-543 10.1124/jpet.107.134882
121. Yoshino, M.; Naka, A.; Sakamoto, Y.; Shibasaki, A.; Toh, M.; Tsukamoto, S.; Kondo, K.; Iida, K. Dietary Isoflavone Daidzein Promotes Tfam Expression That Increases Mitochondrial Biogenesis in C2C12 Muscle Cells J. Nutr. Biochem. 2015, 26 ( 11 ) 1193-1199 10.1016/j.jnutbio.2015.05.010
122. Pons, D. G.; Nadal-Serrano, M.; Blanquer-Rossello, M. M.; Sastre-Serra, J.; Oliver, J.; Roca, P. Genistein Modulates Proliferation and Mitochondrial Functionality in Breast Cancer Cells Depending on ERalpha/ERbeta Ratio J. Cell. Biochem. 2014, 115 ( 5 ) 949-958 10.1002/jcb.24737
123. Xu, X. W.; Shi, C.; He, Z. Q.; Ma, C. M.; Chen, W. H.; Shen, Y. P.; Guo, Q.; Shen, C. J.; Xu, J. Effects of Phytoestrogen on Mitochondrial Structure and Function of Hippocampal CA1 Region of Ovariectomized Rats Cell. Mol. Neurobiol. 2008, 28 ( 6 ) 875-886 10.1007/s10571-008-9265-2
124. Yao, J.; Zhao, L.; Mao, Z.; Chen, S.; Wong, K. C.; To, J.; Brinton, R. D. Potentiation of Brain Mitochondrial Function by S-Equol and R/S-Equol Estrogen Receptor Beta-Selective PhytoSERM Treatments Brain Res. 2013, 1514, 128-141 10.1016/j.brainres.2013.02.021
125. Lee, Y. M.; Choi, J. S.; Kim, M. H.; Jung, M. H.; Lee, Y. S.; Song, J. Effects of Dietary Genistein on Hepatic Lipid Metabolism and Mitochondrial Function in Mice Fed High-Fat Diets Nutrition 2006, 22 ( 9 ) 956-964 10.1016/j.nut.2005.12.014
126. Cederroth, C. R.; Vinciguerra, M.; Gjinovci, A.; Kuhne, F.; Klein, M.; Cederroth, M.; Caille, D.; Suter, M.; Neumann, D.; James, R. W.; Doerge, D. R.; Wallimann, T.; Meda, P.; Foti, M.; Rohner-Jeanrenaud, F.; Vassalli, J. D.; Nef, S. Dietary Phytoestrogens Activate AMP-Activated Protein Kinase with Improvement in Lipid and Glucose Metabolism Diabetes 2008, 57 ( 5 ) 1176-1185 10.2337/db07-0630
127. Stites, T.; Storms, D.; Bauerly, K.; Mah, J.; Harris, C.; Fascetti, A.; Rogers, Q.; Tchaparian, E.; Satre, M.; Rucker, R. B. Pyrroloquinoline Quinone Modulates Mitochondrial Quantity and Function in Mice J. Nutr. 2006, 136 ( 2 ) 390-396
128. Martino Adami, P. V.; Quijano, C.; Magnani, N.; Galeano, P.; Evelson, P.; Cassina, A.; Do Carmo, S.; Leal, M. C.; Castano, E. M.; Cuello, A. C.; Morelli, L. Synaptosomal Bioenergetic Defects Are Associated with Cognitive Impairment in a Transgenic Rat Model of Early Alzheimer’s Disease J. Cereb. Blood Flow Metab. 2015, 10.1177/0271678X15615132
129. Oakes, N. D.; Kennedy, C. J.; Jenkins, A. B.; Laybutt, D. R.; Chisholm, D. J.; Kraegen, E. W. A New Antidiabetic Agent, BRL 49653, Reduces Lipid Availability and Improves Insulin Action and Glucoregulation in the Rat Diabetes 1994, 43 ( 10 ) 1203-1210 10.2337/diabetes.43.10.1203
130. Sohda, T.; Momose, Y.; Meguro, K.; Kawamatsu, Y.; Sugiyama, Y.; Ikeda, H. Studies on Antidiabetic Agents. Synthesis and Hypoglycemic Activity of 5-[4-(Pyridylalkoxy)Benzyl]-2,4-Thiazolidinediones Arzneimittelforschung. 1990, 40 ( 1 ) 37-42
131. Fujiwara, T.; Yoshioka, S.; Yoshioka, T.; Ushiyama, I.; Horikoshi, H. Characterization of New Oral Antidiabetic Agent CS-045. Studies in KK and ob/ob Mice and Zucker Fatty Rats Diabetes 1988, 37 ( 11 ) 1549-1558 10.2337/diab.37.11.1549
132. Fujita, T.; Sugiyama, Y.; Taketomi, S.; Sohda, T.; Kawamatsu, Y.; Iwatsuka, H.; Suzuoki, Z. Reduction of Insulin Resistance in Obese and/or Diabetic Animals by 5-[4-(1-Methylcyclohexylmethoxy)Benzyl]-Thiazolidine-2,4-dione (ADD-3878, U-63,287, Ciglitazone), a New Antidiabetic Agent Diabetes 1983, 32 ( 9 ) 804-810 10.2337/diab.32.9.804
133. Yamagishi, K.; Yamamoto, K.; Mochizuki, Y.; Nakano, T.; Yamada, S.; Tokiwa, H. Flexible Ligand Recognition of Peroxisome Proliferator-Activated Receptor-Gamma (PPARgamma) Bioorg. Med. Chem. Lett. 2010, 20 ( 11 ) 3344-3347 10.1016/j.bmcl.2010.04.031
134. Willson, T. M.; Cobb, J. E.; Cowan, D. J.; Wiethe, R. W.; Correa, I. D.; Prakash, S. R.; Beck, K. D.; Moore, L. B.; Kliewer, S. A.; Lehmann, J. M. The Structure-Activity Relationship between Peroxisome Proliferator-Activated Receptor Gamma Agonism and the Antihyperglycemic Activity of Thiazolidinediones J. Med. Chem. 1996, 39 ( 3 ) 665-668 10.1021/jm950395a
135. Feinstein, D. L.; Spagnolo, A.; Akar, C.; Weinberg, G.; Murphy, P.; Gavrilyuk, V.; Dello Russo, C. Receptor-Independent Actions of PPAR Thiazolidinedione Agonists: Is Mitochondrial Function the Key? Biochem. Pharmacol. 2005, 70 ( 2 ) 177-188 10.1016/j.bcp.2005.03.033
136. LeBrasseur, N. K.; Kelly, M.; Tsao, T. S.; Farmer, S. R.; Saha, A. K.; Ruderman, N. B.; Tomas, E. Thiazolidinediones can Rapidly Activate AMP-Activated Protein Kinase in Mammalian Tissues Am. J. Physiol. Endocrinol. Metab. 2006, 291 ( 1 ) E175-181 10.1152/ajpendo.00453.2005
137. Brunmair, B.; Staniek, K.; Gras, F.; Scharf, N.; Althaym, A.; Clara, R.; Roden, M.; Gnaiger, E.; Nohl, H.; Waldhausl, W.; Furnsinn, C. Thiazolidinediones, Like Metformin, Inhibit Respiratory Complex I: A Common Mechanism Contributing to Their Antidiabetic Actions? Diabetes 2004, 53 ( 4 ) 1052-1059 10.2337/diabetes.53.4.1052
138. Bolten, C. W.; Blanner, P. M.; McDonald, W. G.; Staten, N. R.; Mazzarella, R. A.; Arhancet, G. B.; Meier, M. F.; Weiss, D. J.; Sullivan, P. M.; Hromockyj, A. E.; Kletzien, R. F.; Colca, J. R. Insulin Sensitizing Pharmacology of Thiazolidinediones Correlates with Mitochondrial Gene expression Rather Than Activation of PPAR Gamma Gene Regul. Syst. Bio. 2007, 1, 73-82
139. Miglio, G.; Rosa, A. C.; Rattazzi, L.; Collino, M.; Lombardi, G.; Fantozzi, R. PPARgamma Stimulation Promotes Mitochondrial Biogenesis and Prevents Glucose Deprivation-Induced Neuronal Cell Loss Neurochem. Int. 2009, 55 ( 7 ) 496-504 10.1016/j.neuint.2009.05.001
140. Zolezzi, J. M.; Silva-Alvarez, C.; Ordenes, D.; Godoy, J. A.; Carvajal, F. J.; Santos, M. J.; Inestrosa, N. C. Peroxisome Proliferator-Activated Receptor (PPAR) Gamma and PPARalpha Agonists Modulate Mitochondrial Fusion-Fission Dynamics: Relevance to Reactive Oxygen Species (ROS)-Related Neurodegenerative Disorders? PLoS One 2013, 8 ( 5 ) e64019 10.1371/journal.pone.0064019
141. Quintanilla, R. A.; Jin, Y. N.; Fuenzalida, K.; Bronfman, M.; Johnson, G. V. Rosiglitazone Treatment Prevents Mitochondrial Dysfunction in Mutant Huntingtin-Expressing Cells: Possible Role of Peroxisome Proliferator-Activated Receptor-Gamma (PPARgamma) in the Pathogenesis of Huntington Disease J. Biol. Chem. 2008, 283 ( 37 ) 25628-25637 10.1074/jbc.M804291200
142. Chiang, M. C.; Cheng, Y. C.; Nicol, C. J.; Lin, K. H.; Yen, C. H.; Chen, S. J.; Huang, R. N. Rosiglitazone Activation of PPARgamma-Dependent Signaling is Neuroprotective in Mutant Huntingtin Expressing Cells Exp. Cell Res. 2015, 338 ( 2 ) 183-193 10.1016/j.yexcr.2015.09.005
143. De Nuccio, C.; Bernardo, A.; Cruciani, C.; De Simone, R.; Visentin, S.; Minghetti, L. Peroxisome Proliferator Activated Receptor-Gamma Agonists Protect Oligodendrocyte Progenitors against Tumor Necrosis Factor-Alpha-Induced Damage: Effects on Mitochondrial Functions and Differentiation Exp. Neurol. 2015, 271, 506-514 10.1016/j.expneurol.2015.07.014
144. Strum, J. C.; Shehee, R.; Virley, D.; Richardson, J.; Mattie, M.; Selley, P.; Ghosh, S.; Nock, C.; Saunders, A.; Roses, A. Rosiglitazone Induces Mitochondrial Biogenesis in Mouse Brain J. Alzheimers Dis. 2007, 11 ( 1 ) 45-51
145. Sauerbeck, A.; Gao, J.; Readnower, R.; Liu, M.; Pauly, J. R.; Bing, G.; Sullivan, P. G. Pioglitazone Attenuates Mitochondrial Dysfunction, Cognitive Impairment, Cortical Tissue Loss, and Inflammation Following Traumatic Brain Injury Exp. Neurol. 2011, 227 ( 1 ) 128-135 10.1016/j.expneurol.2010.10.003
146. Drosatos, K.; Khan, R. S.; Trent, C. M.; Jiang, H.; Son, N. H.; Blaner, W. S.; Homma, S.; Schulze, P. C.; Goldberg, I. J. Peroxisome Proliferator-Activated Receptor-Gamma Activation Prevents Sepsis-Related Cardiac Dysfunction and Mortality in Mice Circ.: Heart Failure 2013, 6 ( 3 ) 550-562 10.1161/CIRCHEARTFAILURE.112.000177
147. He, H.; Tao, H.; Xiong, H.; Duan, S. Z.; McGowan, F. X., Jr.; Mortensen, R. M.; Balschi, J. A. Rosiglitazone Causes Cardiotoxicity via Peroxisome Proliferator-Activated Receptor Gamma-Independent Mitochondrial Oxidative Stress in Mouse Hearts Toxicol. Sci. 2014, 138 ( 2 ) 468-481 10.1093/toxsci/kfu015
148. Palee, S.; Weerateerangkul, P.; Surinkeaw, S.; Chattipakorn, S.; Chattipakorn, N. Effect of Rosiglitazone on Cardiac Electrophysiology, Infarct Size and Mitochondrial Function in Ischaemia and Reperfusion of Swine and Rat Heart Exp. Physiol. 2011, 96 ( 8 ) 778-789 10.1113/expphysiol.2011.057885
149. Mercer, S. W.; Trayhurn, P. Effects of Ciglitazone on Insulin Resistance and Thermogenic Responsiveness to Acute Cold in Brown Adipose Tissue of Genetically Obese (ob/ob) Mice FEBS Lett. 1986, 195 ( 1-2 ) 12-16 10.1016/0014-5793(86)80120-X
150. Bruin, J. E.; Petrik, J. J.; Hyslop, J. R.; Raha, S.; Tarnopolsky, M. A.; Gerstein, H. C.; Holloway, A. C. Rosiglitazone Improves Pancreatic Mitochondrial Function in an Animal Model of Dysglycemia: Role of the Insulin-Like Growth Factor Axis Endocrine 2010, 37 ( 2 ) 303-311 10.1007/s12020-009-9294-8
151. Takada, S.; Hirabayashi, K.; Kinugawa, S.; Yokota, T.; Matsushima, S.; Suga, T.; Kadoguchi, T.; Fukushima, A.; Homma, T.; Mizushima, W.; Masaki, Y.; Furihata, T.; Katsuyama, R.; Okita, K.; Tsutsui, H. Pioglitazone Ameliorates the Lowered Exercise Capacity and Impaired Mitochondrial Function of the Skeletal Muscle in Type 2 Diabetic Mice Eur. J. Pharmacol. 2014, 740, 690-696 10.1016/j.ejphar.2014.06.008
152. Bogacka, I.; Xie, H.; Bray, G. A.; Smith, S. R. Pioglitazone Induces Mitochondrial Biogenesis in Human Subcutaneous Adipose Tissue In Vivo Diabetes 2005, 54 ( 5 ) 1392-1399 10.2337/diabetes.54.5.1392
153. Mensink, M.; Hesselink, M. K.; Russell, A. P.; Schaart, G.; Sels, J. P.; Schrauwen, P. Improved Skeletal Muscle Oxidative Enzyme Activity and Restoration of PGC-1 Alpha and PPAR Beta/Delta Gene Expression upon Rosiglitazone Treatment in Obese Patients with Type 2 Diabetes Mellitus Int. J. Obes. 2007, 31 ( 8 ) 1302-1310 10.1038/sj.ijo.0803567
154. Sbert-Roig, M.; Bauza-Thorbrugge, M.; Galmes-Pascual, B. M.; Capllonch-Amer, G.; Garcia-Palmer, F. J.; Llado, I.; Proenza, A. M.; Gianotti, M. GPER Mediates the Effects of 17beta-Estradiol in Cardiac Mitochondrial Biogenesis and Function Mol. Cell. Endocrinol. 2016, 420, 116-124 10.1016/j.mce.2015.11.027
155. Thayer, S. A.; Doisy, E. A.; Doisy, E. A. The Bio-Assay of Beta-Estradiol Yale J. Biol. Med. 1944, 17 ( 1 ) 19-26
156. Johnson, W. S.; Gravestock, M. B.; McCarry, B. E. Acetylenic Bond Participation in Biogenetic-Like Olefinic Cyclizations. II. Synthesis of dl-Progesterone J. Am. Chem. Soc. 1971, 93 ( 17 ) 4332-4334 10.1021/ja00746a062
157. Brzozowski, A. M.; Pike, A. C.; Dauter, Z.; Hubbard, R. E.; Bonn, T.; Engstrom, O.; Ohman, L.; Greene, G. L.; Gustafsson, J. A.; Carlquist, M. Molecular Basis of Agonism and Antagonism in the Oestrogen Receptor Nature 1997, 389 ( 6652 ) 753-758 10.1038/39645
158. Stauffer, S. R.; Coletta, C. J.; Tedesco, R.; Nishiguchi, G.; Carlson, K.; Sun, J.; Katzenellenbogen, B. S.; Katzenellenbogen, J. A. Pyrazole Ligands: Structure-Affinity/Activity Relationships and Estrogen Receptor-Alpha-Selective Agonists J. Med. Chem. 2000, 43 ( 26 ) 4934-4947 10.1021/jm000170m
159. Meyers, M. J.; Sun, J.; Carlson, K. E.; Marriner, G. A.; Katzenellenbogen, B. S.; Katzenellenbogen, J. A. Estrogen Receptor-Beta Potency-Selective Ligands: Structure-Activity Relationship Studies of Diarylpropionitriles and Their Acetylene and Polar Analogues J. Med. Chem. 2001, 44 ( 24 ) 4230-4251 10.1021/jm010254a
160. Bologa, C. G.; Revankar, C. M.; Young, S. M.; Edwards, B. S.; Arterburn, J. B.; Kiselyov, A. S.; Parker, M. A.; Tkachenko, S. E.; Savchuck, N. P.; Sklar, L. A.; Oprea, T. I.; Prossnitz, E. R. Virtual and Biomolecular Screening Converge on a Selective Agonist for GPR30 Nat. Chem. Biol. 2006, 2 ( 4 ) 207-212 10.1038/nchembio775
161. Arnatt, C. K.; Zhang, Y. G Protein-Coupled Estrogen Receptor (GPER) Agonist Dual Binding Mode Analyses toward Understanding of Its Activation Mechanism: A Comparative Homology Modeling Approach Mol. Inf. 2013, 32 ( 7 ) 647-658 10.1002/minf.201200136
162. Mendez-Luna, D.; Martinez-Archundia, M.; Maroun, R. C.; Ceballos-Reyes, G.; Fragoso-Vazquez, M. J.; Gonzalez-Juarez, D. E.; Correa-Basurto, J. Deciphering the GPER/GPR30-Agonist and Antagonists Interactions Using Molecular Modeling Studies, Molecular Dynamics, and Docking Simulations J. Biomol. Struct. Dyn. 2015, 33 ( 10 ) 2161-2172 10.1080/07391102.2014.994102
163. Mattingly, K. A.; Ivanova, M. M.; Riggs, K. A.; Wickramasinghe, N. S.; Barch, M. J.; Klinge, C. M. Estradiol Stimulates Transcription of Nuclear Respiratory Factor-1 and Increases Mitochondrial Biogenesis Mol. Endocrinol. 2008, 22 ( 3 ) 609-622 10.1210/me.2007-0029
164. Giordano, C.; Montopoli, M.; Perli, E.; Orlandi, M.; Fantin, M.; Ross-Cisneros, F. N.; Caparrotta, L.; Martinuzzi, A.; Ragazzi, E.; Ghelli, A.; Sadun, A. A.; d’Amati, G.; Carelli, V. Oestrogens Ameliorate Mitochondrial Dysfunction in Leber’s Hereditary Optic Neuropathy Brain 2011, 134 ( 1 ) 220-234 10.1093/brain/awq276
165. Irwin, R. W.; Yao, J.; Hamilton, R. T.; Cadenas, E.; Brinton, R. D.; Nilsen, J. Progesterone and Estrogen Regulate Oxidative Metabolism in Brain Mitochondria Endocrinology 2008, 149 ( 6 ) 3167-3175 10.1210/en.2007-1227
166. Irwin, R. W.; Yao, J.; To, J.; Hamilton, R. T.; Cadenas, E.; Brinton, R. D. Selective Oestrogen Receptor Modulators Differentially Potentiate Brain Mitochondrial Function J. Neuroendocrinol. 2012, 24 ( 1 ) 236-248 10.1111/j.1365-2826.2011.02251.x
167. Milne, J. C.; Lambert, P. D.; Schenk, S.; Carney, D. P.; Smith, J. J.; Gagne, D. J.; Jin, L.; Boss, O.; Perni, R. B.; Vu, C. B.; Bemis, J. E.; Xie, R.; Disch, J. S.; Ng, P. Y.; Nunes, J. J.; Lynch, A. V.; Yang, H.; Galonek, H.; Israelian, K.; Choy, W.; Iffland, A.; Lavu, S.; Medvedik, O.; Sinclair, D. A.; Olefsky, J. M.; Jirousek, M. R.; Elliott, P. J.; Westphal, C. H. Small Molecule Activators of SIRT1 as Therapeutics for the Treatment of Type 2 Diabetes Nature 2007, 450 ( 7170 ) 712-716 10.1038/nature06261
168. Hoffmann, E.; Wald, J.; Lavu, S.; Roberts, J.; Beaumont, C.; Haddad, J.; Elliott, P.; Westphal, C.; Jacobson, E. Pharmacokinetics and Tolerability of SRT2104, a First-In-Class Small Molecule Activator of SIRT1, after Single and Repeated Oral Administration in Man Br. J. Clin. Pharmacol. 2013, 75 ( 1 ) 186-196 10.1111/j.1365-2125.2012.04340.x
169. Vu, C. B.; Bemis, J. E.; Disch, J. S.; Ng, P. Y.; Nunes, J. J.; Milne, J. C.; Carney, D. P.; Lynch, A. V.; Smith, J. J.; Lavu, S.; Lambert, P. D.; Gagne, D. J.; Jirousek, M. R.; Schenk, S.; Olefsky, J. M.; Perni, R. B. Discovery of Imidazo[1,2-b]Thiazole Derivatives as Novel SIRT1 Activators J. Med. Chem. 2009, 52 ( 5 ) 1275-1283 10.1021/jm8012954
170. Pacholec, M.; Bleasdale, J. E.; Chrunyk, B.; Cunningham, D.; Flynn, D.; Garofalo, R. S.; Griffith, D.; Griffor, M.; Loulakis, P.; Pabst, B.; Qiu, X.; Stockman, B.; Thanabal, V.; Varghese, A.; Ward, J.; Withka, J.; Ahn, K. SRT1720, SRT2183, SRT1460, and Resveratrol Are Not Direct Activators of SIRT1 J. Biol. Chem. 2010, 285 ( 11 ) 8340-8351 10.1074/jbc.M109.088682
171. Hubbard, B. P.; Gomes, A. P.; Dai, H.; Li, J.; Case, A. W.; Considine, T.; Riera, T. V.; Lee, J. E.; E, S. Y.; Lamming, D. W.; Pentelute, B. L.; Schuman, E. R.; Stevens, L. A.; Ling, A. J.; Armour, S. M.; Michan, S.; Zhao, H.; Jiang, Y.; Sweitzer, S. M.; Blum, C. A.; Disch, J. S.; Ng, P. Y.; Howitz, K. T.; Rolo, A. P.; Hamuro, Y.; Moss, J.; Perni, R. B.; Ellis, J. L.; Vlasuk, G. P.; Sinclair, D. A. Evidence for a Common Mechanism of SIRT1 Regulation by Allosteric Activators Science 2013, 339 ( 6124 ) 1216-1219 10.1126/science.1231097
172. Minor, R. K.; Baur, J. A.; Gomes, A. P.; Ward, T. M.; Csiszar, A.; Mercken, E. M.; Abdelmohsen, K.; Shin, Y. K.; Canto, C.; Scheibye-Knudsen, M.; Krawczyk, M.; Irusta, P. M.; Martin-Montalvo, A.; Hubbard, B. P.; Zhang, Y.; Lehrmann, E.; White, A. A.; Price, N. L.; Swindell, W. R.; Pearson, K. J.; Becker, K. G.; Bohr, V. A.; Gorospe, M.; Egan, J. M.; Talan, M. I.; Auwerx, J.; Westphal, C. H.; Ellis, J. L.; Ungvari, Z.; Vlasuk, G. P.; Elliott, P. J.; Sinclair, D. A.; de Cabo, R. SRT1720 Improves Survival and Healthspan of Obese Mice Sci. Rep. 2011, 1, 70 10.1038/srep00070
173. Feige, J. N.; Lagouge, M.; Canto, C.; Strehle, A.; Houten, S. M.; Milne, J. C.; Lambert, P. D.; Mataki, C.; Elliott, P. J.; Auwerx, J. Specific SIRT1 Activation Mimics Low Energy Levels and Protects against Diet-Induced Metabolic Disorders by Enhancing Fat Oxidation Cell Metab. 2008, 8 ( 5 ) 347-358 10.1016/j.cmet.2008.08.017
174. Mercken, E. M.; Mitchell, S. J.; Martin-Montalvo, A.; Minor, R. K.; Almeida, M.; Gomes, A. P.; Scheibye-Knudsen, M.; Palacios, H. H.; Licata, J. J.; Zhang, Y.; Becker, K. G.; Khraiwesh, H.; Gonzalez-Reyes, J. A.; Villalba, J. M.; Baur, J. A.; Elliott, P.; Westphal, C.; Vlasuk, G. P.; Ellis, J. L.; Sinclair, D. A.; Bernier, M.; de Cabo, R. SRT2104 Extends Survival of Male Mice on a Standard Diet and Preserves Bone and Muscle Mass Aging Cell 2014, 13 ( 5 ) 787-796 10.1111/acel.12220
175. Xiang, Z.; Krainc, D. Pharmacological Upregulation of PGC1alpha in Oligodendrocytes: Implications for Huntington’s Disease J. Huntingtons Dis. 2013, 2 ( 1 ) 101-105 10.3233/JHD-130046
176. Jiang, M.; Zheng, J.; Peng, Q.; Hou, Z.; Zhang, J.; Mori, S.; Ellis, J. L.; Vlasuk, G. P.; Fries, H.; Suri, V.; Duan, W. Sirtuin 1 Activator SRT2104 Protects Huntington’s Disease Mice Ann. Clin. Transl. Neurol. 2014, 1 ( 12 ) 1047-1052 10.1002/acn3.135
177. Funk, J. A.; Odejinmi, S.; Schnellmann, R. G. SRT1720 Induces Mitochondrial Biogenesis and Rescues Mitochondrial Function after Oxidant Injury in Renal Proximal Tubule Cells J. Pharmacol. Exp. Ther. 2010, 333 ( 2 ) 593-601 10.1124/jpet.109.161992
178. Khader, A.; Yang, W. L.; Kuncewitch, M.; Jacob, A.; Prince, J. M.; Asirvatham, J. R.; Nicastro, J.; Coppa, G. F.; Wang, P. Sirtuin 1 Activation Stimulates Mitochondrial Biogenesis and Attenuates Renal Injury after Ischemia-Reperfusion Transplantation 2014, 98 ( 2 ) 148-156 10.1097/TP.0000000000000194
179. He, W.; Wang, Y.; Zhang, M. Z.; You, L.; Davis, L. S.; Fan, H.; Yang, H. C.; Fogo, A. B.; Zent, R.; Harris, R. C.; Breyer, M. D.; Hao, C. M. Sirt1 Activation Protects the Mouse Renal Medulla from Oxidative Injury J. Clin. Invest. 2010, 120 ( 4 ) 1056-1068 10.1172/JCI41563
180. Tong, C.; Morrison, A.; Mattison, S.; Qian, S.; Bryniarski, M.; Rankin, B.; Wang, J.; Thomas, D. P.; Li, J. Impaired SIRT1 Nucleocytoplasmic Shuttling in the Senescent Heart during Ischemic Stress FASEB J. 2013, 27 ( 11 ) 4332-4342 10.1096/fj.12-216473
181. Zhang, Y.; Mi, S. L.; Hu, N.; Doser, T. A.; Sun, A.; Ge, J.; Ren, J. Mitochondrial Aldehyde Dehydrogenase 2 Accentuates Aging-Induced Cardiac Remodeling and Contractile Dysfunction: Role of AMPK, Sirt1, and Mitochondrial Function Free Radical Biol. Med. 2014, 71, 208-220 10.1016/j.freeradbiomed.2014.03.018
182. Gano, L. B.; Donato, A. J.; Pasha, H. M.; Hearon, C. M., Jr.; Sindler, A. L.; Seals, D. R. The SIRT1 Activator SRT1720 Reverses Vascular Endothelial Dysfunction, Excessive Superoxide Production, and Inflammation with Aging in Mice Am. J. Physiol. Heart Circ. Physiol. 2014, 307 ( 12 ) H1754-1763 10.1152/ajpheart.00377.2014
183. Mitchell, S. J.; Martin-Montalvo, A.; Mercken, E. M.; Palacios, H. H.; Ward, T. M.; Abulwerdi, G.; Minor, R. K.; Vlasuk, G. P.; Ellis, J. L.; Sinclair, D. A.; Dawson, J.; Allison, D. B.; Zhang, Y.; Becker, K. G.; Bernier, M.; de Cabo, R. The SIRT1 Activator SRT1720 Extends Lifespan and Improves Health of Mice Fed a Standard Diet Cell Rep. 2014, 6 ( 5 ) 836-843 10.1016/j.celrep.2014.01.031
184. Baksi, A.; Kraydashenko, O.; Zalevkaya, A.; Stets, R.; Elliott, P.; Haddad, J.; Hoffmann, E.; Vlasuk, G. P.; Jacobson, E. W. A phase II, Randomized, Placebo-Controlled, Double-Blind, Multi-Dose Study of SRT2104, a SIRT1 Activator, in Subjects with Type 2 Diabetes Br. J. Clin. Pharmacol. 2014, 78 ( 1 ) 69-77 10.1111/bcp.12327
185. Venkatasubramanian, S.; Noh, R. M.; Daga, S.; Langrish, J. P.; Joshi, N. V.; Mills, N. L.; Hoffmann, E.; Jacobson, E. W.; Vlasuk, G. P.; Waterhouse, B. R.; Lang, N. N.; Newby, D. E. Cardiovascular Effects of a Novel SIRT1 Activator, SRT2104, in Otherwise Healthy Cigarette Smokers J. Am. Heart Assoc. 2013, 2 ( 3 ) e000042 10.1161/JAHA.113.000042
186. Reznick, R. M.; Zong, H.; Li, J.; Morino, K.; Moore, I. K.; Yu, H. J.; Liu, Z. X.; Dong, J.; Mustard, K. J.; Hawley, S. A.; Befroy, D.; Pypaert, M.; Hardie, D. G.; Young, L. H.; Shulman, G. I. Aging-Associated Reductions in AMP-Activated Protein Kinase Activity and Mitochondrial Biogenesis Cell Metab. 2007, 5 ( 2 ) 151-156 10.1016/j.cmet.2007.01.008
187. Suwa, M.; Nakano, H.; Radak, Z.; Kumagai, S. Short-Term Adenosine Monophosphate-Activated Protein Kinase Activator 5-Aminoimidazole-4-Carboxamide-1-Beta-D-Ribofuranoside Treatment Increases the Sirtuin 1 Protein Expression in Skeletal Muscle Metab., Clin. Exp. 2011, 60 ( 3 ) 394-403 10.1016/j.metabol.2010.03.003
188. Zhang, L.; Frederich, M.; He, H.; Balschi, J. A. Relationship Between 5-Aminoimidazole-4-Carboxamide-Ribotide and AMP-Activated Protein Kinase Activity in the Perfused Mouse Heart Am. J. Physiol. Heart Circ. Physiol. 2006, 290 ( 3 ) H1235-1243 10.1152/ajpheart.00906.2005
189. Sterne, J. [Treatment of Diabetes Mellitus with N,N-Dimethylguanylguanidine (LA. 6023, Glucophage)] Therapie 1959, 14, 625-630
190. Ungar, G.; Freedman, L.; Shapiro, S. L. Pharmacological Studies of a New Oral Hypoglycemic Drug Exp. Biol. Med. 1957, 95 ( 1 ) 190-192 10.3181/00379727-95-23163
191. Jenkins, Y.; Sun, T. Q.; Markovtsov, V.; Foretz, M.; Li, W.; Nguyen, H.; Li, Y.; Pan, A.; Uy, G.; Gross, L.; Baltgalvis, K.; Yung, S. L.; Gururaja, T.; Kinoshita, T.; Owyang, A.; Smith, I. J.; McCaughey, K.; White, K.; Godinez, G.; Alcantara, R.; Choy, C.; Ren, H.; Basile, R.; Sweeny, D. J.; Xu, X.; Issakani, S. D.; Carroll, D. C.; Goff, D. A.; Shaw, S. J.; Singh, R.; Boros, L. G.; Laplante, M. A.; Marcotte, B.; Kohen, R.; Viollet, B.; Marette, A.; Payan, D. G.; Kinsella, T. M.; Hitoshi, Y. AMPK Activation through Mitochondrial Regulation Results in Increased Substrate Oxidation and Improved Metabolic Parameters in Models of Diabetes PLoS One 2013, 8 ( 12 ) e81870 10.1371/journal.pone.0081870
192. Li, Y. Y.; Yu, L. F.; Zhang, L. N.; Qiu, B. Y.; Su, M. B.; Wu, F.; Chen, D. K.; Pang, T.; Gu, M.; Zhang, W.; Ma, W. P.; Jiang, H. W.; Li, J. Y.; Nan, F. J.; Li, J. Novel Small-Molecule AMPK Activator Orally Exerts Beneficial Effects on Diabetic db/db Mice Toxicol. Appl. Pharmacol. 2013, 273 ( 2 ) 325-334 10.1016/j.taap.2013.09.006
193. Cool, B.; Zinker, B.; Chiou, W.; Kifle, L.; Cao, N.; Perham, M.; Dickinson, R.; Adler, A.; Gagne, G.; Iyengar, R.; Zhao, G.; Marsh, K.; Kym, P.; Jung, P.; Camp, H. S.; Frevert, E. Identification and Characterization of a Small Molecule AMPK Activator That Treats Key Components of Type 2 Diabetes and the Metabolic Syndrome Cell Metab. 2006, 3 ( 6 ) 403-416 10.1016/j.cmet.2006.05.005
194. Golubitzky, A.; Dan, P.; Weissman, S.; Link, G.; Wikstrom, J. D.; Saada, A. Screening for Active Small Molecules in Mitochondrial Complex I Deficient Patient’s Fibroblasts, Reveals AICAR as the Most Beneficial Compound PLoS One 2011, 6 ( 10 ) e26883 10.1371/journal.pone.0026883
195. Garrido-Maraver, J.; Paz, M. V.; Cordero, M. D.; Bautista-Lorite, J.; Oropesa-Avila, M.; de la Mata, M.; Pavon, A. D.; de Lavera, I.; Alcocer-Gomez, E.; Galan, F.; Ybot Gonzalez, P.; Cotan, D.; Jackson, S.; Sanchez-Alcazar, J. A. Critical Role of AMP-Activated Protein Kinase in the Balance Between Mitophagy and Mitochondrial Biogenesis in MELAS Disease Biochim. Biophys. Acta, Mol. Basis Dis. 2015, 1852 ( 11 ) 2535-2553 10.1016/j.bbadis.2015.08.027
196. Shaw, R. J.; Lamia, K. A.; Vasquez, D.; Koo, S. H.; Bardeesy, N.; Depinho, R. A.; Montminy, M.; Cantley, L. C. The Kinase LKB1Mediates Glucose Homeostasis in Liver and Therapeutic Effects of Metformin Science 2005, 310 ( 5754 ) 1642-1646 10.1126/science.1120781
197. Sanders, M. J.; Ali, Z. S.; Hegarty, B. D.; Heath, R.; Snowden, M. A.; Carling, D. Defining the Mechanism of Activation of AMP-Activated Protein Kinase by the Small Molecule A-769662, a Member of the Thienopyridone family J. Biol. Chem. 2007, 282 ( 45 ) 32539-32548 10.1074/jbc.M706543200
198. Dugan, L. L.; You, Y. H.; Ali, S. S.; Diamond-Stanic, M.; Miyamoto, S.; DeCleves, A. E.; Andreyev, A.; Quach, T.; Ly, S.; Shekhtman, G.; Nguyen, W.; Chepetan, A.; Le, T. P.; Wang, L.; Xu, M.; Paik, K. P.; Fogo, A.; Viollet, B.; Murphy, A.; Brosius, F.; Naviaux, R. K.; Sharma, K. AMPK Dysregulation Promotes Diabetes-Related Reduction of Superoxide and Mitochondrial Function J. Clin. Invest. 2013, 123 ( 11 ) 4888-4899 10.1172/JCI66218
199. Wang, X. R.; Zhang, M. W.; Chen, D. D.; Zhang, Y.; Chen, A. F. AMP-Activated Protein Kinase Rescues the Angiogenic Functions of Endothelial Progenitor Cells via Manganese Superoxide Dismutase Induction in Type 1 Diabetes Am. J. Physiol. Endocrinol. Metab. 2011, 300 ( 6 ) E1135-1145 10.1152/ajpendo.00001.2011
200. Xie, Z.; Zhang, J.; Wu, J.; Viollet, B.; Zou, M. H. Upregulation of Mitochondrial Uncoupling Protein-2 by the AMP-Activated Protein Kinase in Endothelial Cells Attenuates Oxidative Stress in Diabetes Diabetes 2008, 57 ( 12 ) 3222-3230 10.2337/db08-0610
201. Pold, R.; Jensen, L. S.; Jessen, N.; Buhl, E. S.; Schmitz, O.; Flyvbjerg, A.; Fujii, N.; Goodyear, L. J.; Gotfredsen, C. F.; Brand, C. L.; Lund, S. Long-Term AICAR Administration and Exercise Prevents Diabetes in ZDF Rats Diabetes 2005, 54 ( 4 ) 928-934 10.2337/diabetes.54.4.928
202. Boon, H.; Bosselaar, M.; Praet, S. F.; Blaak, E. E.; Saris, W. H.; Wagenmakers, A. J.; McGee, S. L.; Tack, C. J.; Smits, P.; Hargreaves, M.; van Loon, L. J. Intravenous AICAR Administration Reduces Hepatic Glucose Output and Inhibits Whole Body Lipolysis in Type 2 Diabetic Patients Diabetologia 2008, 51 ( 10 ) 1893-1900 10.1007/s00125-008-1108-7
203. Liong, S.; Lappas, M. Activation of AMPK Improves Inflammation and Insulin Resistance in Adipose Tissue and Skeletal Muscle from Pregnant Women J. Physiol. Biochem. 2015, 71 ( 4 ) 703-717 10.1007/s13105-015-0435-7
204. Bikman, B. T.; Zheng, D.; Reed, M. A.; Hickner, R. C.; Houmard, J. A.; Dohm, G. L. Lipid-Induced Insulin Resistance Is Prevented in Lean and Obese Myotubes by AICAR Treatment Am. J. Physiol. Regul. Integr. Comp. Physiol. 2010, 298 ( 6 ) R1692-1699 10.1152/ajpregu.00190.2009
205. Yang, C.; Xu, H.; Cai, L.; Du, X.; Jiang, Y.; Zhang, Y.; Zhou, H.; Chen, Z. K. Donor Pretreatment with Adenosine Monophosphate-Activated Protein Kinase Activator Protects Cardiac Grafts from Cold Ischaemia/Reperfusion Injury Eur. J. Cardiothorac. Surg. 2016, 49 ( 5 ) 1354-1360 10.1093/ejcts/ezv413
206. Yu, L.; Yang, S. J. AMP-Activated Protein Kinase Mediates Activity-Dependent Regulation of Peroxisome Proliferator-Activated Receptor Gamma Coactivator-1alpha and Nuclear Respiratory Factor 1 Expression in Rat Visual Cortical Neurons Neuroscience 2010, 169 ( 1 ) 23-38 10.1016/j.neuroscience.2010.04.063
207. Tao, K.; Matsuki, N.; Koyama, R. AMP-Activated Protein Kinase Mediates Activity-Dependent Axon Branching by Recruiting Mitochondria to Axon Dev. Neurobiol. 2014, 74 ( 6 ) 557-573 10.1002/dneu.22149
208. Du, L. L.; Chai, D. M.; Zhao, L. N.; Li, X. H.; Zhang, F. C.; Zhang, H. B.; Liu, L. B.; Wu, K.; Liu, R.; Wang, J. Z.; Zhou, X. W. AMPK Activation Ameliorates Alzheimer’s Disease-Like Pathology and Spatial Memory Impairment in a Streptozotocin-Induced Alzheimer’s Disease Model in Rats J. Alzheimers Dis. 2015, 43 ( 3 ) 775-784 10.3233/JAD-140564
209. Kim, J.; Park, Y. J.; Jang, Y.; Kwon, Y. H. AMPK Activation Inhibits Apoptosis and Tau Hyperphosphorylation Mediated by Palmitate in SH-SY5Y Cells Brain Res. 2011, 1418, 42-51 10.1016/j.brainres.2011.08.059
210. Greco, S. J.; Sarkar, S.; Johnston, J. M.; Tezapsidis, N. Leptin Regulates Tau Phosphorylation and Amyloid through AMPK in Neuronal Cells Biochem. Biophys. Res. Commun. 2009, 380 ( 1 ) 98-104 10.1016/j.bbrc.2009.01.041
211. Clough-Helfman, C.; Phillis, J. W. 5-Aminoimidazole-4-Carboxamide Riboside (AICAR) Administration Reduces Cerebral Ischemic Damage in the Mongolian Gerbil Brain Res. Bull. 1990, 25 ( 1 ) 203-206 10.1016/0361-9230(90)90277-7
212. Roskoski, R., Jr. ERK1/2 MAP Kinases: Structure, Function, and Regulation Pharmacol. Res. 2012, 66 ( 2 ) 105-143 10.1016/j.phrs.2012.04.005
213. Duncia, J. V.; Santella, J. B., 3rd; Higley, C. A.; Pitts, W. J.; Wityak, J.; Frietze, W. E.; Rankin, F. W.; Sun, J. H.; Earl, R. A.; Tabaka, A. C.; Teleha, C. A.; Blom, K. F.; Favata, M. F.; Manos, E. J.; Daulerio, A. J.; Stradley, D. A.; Horiuchi, K.; Copeland, R. A.; Scherle, P. A.; Trzaskos, J. M.; Magolda, R. L.; Trainor, G. L.; Wexler, R. R.; Hobbs, F. W.; Olson, R. E. MEK Inhibitors: The Chemistry and Biological Activity of U0126, Its Analogs, and Cyclization Products Bioorg. Med. Chem. Lett. 1998, 8 ( 20 ) 2839-2844 10.1016/S0960-894X(98)00522-8
214. Abe, H.; Kikuchi, S.; Hayakawa, K.; Iida, T.; Nagahashi, N.; Maeda, K.; Sakamoto, J.; Matsumoto, N.; Miura, T.; Matsumura, K.; Seki, N.; Inaba, T.; Kawasaki, H.; Yamaguchi, T.; Kakefuda, R.; Nanayama, T.; Kurachi, H.; Hori, Y.; Yoshida, T.; Kakegawa, J.; Watanabe, Y.; Gilmartin, A. G.; Richter, M. C.; Moss, K. G.; Laquerre, S. G. Discovery of a Highly Potent and Selective MEK Inhibitor: GSK1120212 (JTP-74057 DMSO Solvate) ACS Med. Chem. Lett. 2011, 2 ( 4 ) 320-324 10.1021/ml200004g
215. Haq, R.; Shoag, J.; Andreu-Perez, P.; Yokoyama, S.; Edelman, H.; Rowe, G. C.; Frederick, D. T.; Hurley, A. D.; Nellore, A.; Kung, A. L.; Wargo, J. A.; Song, J. S.; Fisher, D. E.; Arany, Z.; Widlund, H. R. Oncogenic BRAF Regulates Oxidative Metabolism via PGC1alpha and MITF Cancer Cell 2013, 23 ( 3 ) 302-315 10.1016/j.ccr.2013.02.003
216. Wang, K. Z.; Zhu, J.; Dagda, R. K.; Uechi, G.; Cherra, S. J., 3rd; Gusdon, A. M.; Balasubramani, M.; Chu, C. T. ERK-Mediated Phosphorylation of TFAM Downregulates Mitochondrial Transcription: Implications for Parkinson’s Disease Mitochondrion 2014, 17, 132-140 10.1016/j.mito.2014.04.008
217. Nowak, G.; Clifton, G. L.; Godwin, M. L.; Bakajsova, D. Activation of ERK1/2 Pathway Mediates Oxidant-Induced Decreases in Mitochondrial Function in Renal Cells Am. J. Physiol. Renal Physiol. 2006, 291 ( 4 ) F840-855 10.1152/ajprenal.00219.2005
218. Smith, J. A.; Stallons, L. J.; Collier, J. B.; Chavin, K. D.; Schnellmann, R. G. Suppression of Mitochondrial Biogenesis through Toll-Like Receptor 4-Dependent Mitogen-Activated Protein Kinase Kinase/Extracellular Signal-Regulated Kinase Signaling in Endotoxin-Induced Acute Kidney Injury J. Pharmacol. Exp. Ther. 2015, 352 ( 2 ) 346-357 10.1124/jpet.114.221085
219. Field, L.; Dilts, R. V.; Ravichandran, R.; Lenhert, P. G.; Carnahan, G. E. An Unusually Stable Thionitrite from N-Acetyl-D,L-Penicillamine; X-Ray Crystal and Molecular Structure of 2-(Acetylamino)-2-Carboxy-1,1-Dimethylethyl Thionitrite J. Chem. Soc., Chem. Commun. 1978, 6 ) 249-250 10.1039/c39780000249
220. Hrabie, J. A.; Klose, J. R.; Wink, D. A.; Keefer, L. K. New Nitric Oxide-Releasing Zwitterions Derived from Polyamines J. Org. Chem. 1993, 58 ( 6 ) 1472-1476 10.1021/jo00058a030
221. Stasch, J. P.; Schmidt, P.; Alonso-Alija, C.; Apeler, H.; Dembowsky, K.; Haerter, M.; Heil, M.; Minuth, T.; Perzborn, E.; Pleiss, U.; Schramm, M.; Schroeder, W.; Schroder, H.; Stahl, E.; Steinke, W.; Wunder, F. NO-and Haem-Independent Activation of Soluble Guanylyl Cyclase: Molecular Basis and Cardiovascular Implications of a New Pharmacological Principle Br. J. Pharmacol. 2002, 136 ( 5 ) 773-783 10.1038/sj.bjp.0704778
222. Mittendorf, J.; Weigand, S.; Alonso-Alija, C.; Bischoff, E.; Feurer, A.; Gerisch, M.; Kern, A.; Knorr, A.; Lang, D.; Muenter, K.; Radtke, M.; Schirok, H.; Schlemmer, K. H.; Stahl, E.; Straub, A.; Wunder, F.; Stasch, J. P. Discovery of Riociguat (BAY 63-2521): A Potent, Oral Stimulator of Soluble Guanylate Cyclase for the Treatment of Pulmonary Hypertension ChemMedChem 2009, 4 ( 5 ) 853-865 10.1002/cmdc.200900014
223. Straub, A.; Stasch, J. P.; Alonso-Alija, C.; Benet-Buchholz, J.; Ducke, B.; Feurer, A.; Furstner, C. NO-Independent Stimulators of Soluble Guanylate Cyclase Bioorg. Med. Chem. Lett. 2001, 11 ( 6 ) 781-784 10.1016/S0960-894X(01)00073-7
224. Bergstrand, H.; Kristoffersson, J.; Lundquist, B.; Schurmann, A. Effects of Antiallergic Agents, Compound 48/80, and Some Reference Inhibitors on the Activity of Partially Purified Human Lung Tissue Adenosine Cyclic 3′,5′-Monophosphate and Guanosine Cyclic 3′,5′-Monophosphate Phosphodiesterases Mol. Pharmacol. 1977, 13 ( 1 ) 38-43
225. Boolell, M.; Allen, M. J.; Ballard, S. A.; Gepi-Attee, S.; Muirhead, G. J.; Naylor, A. M.; Osterloh, I. H.; Gingell, C. Sildenafil: An Orally Active Type 5 Cyclic GMP-Specific Phosphodiesterase Inhibitor for the Treatment of Penile Erectile Dysfunction Int. J. Impot. Res. 1996, 8 ( 2 ) 47-52
226. Doh, H.; Shin, C. Y.; Son, M.; Ko, J. I.; Yoo, M.; Kim, S. H.; Kim, W. B. Mechanism of Erectogenic Effect of the Selective Phosphodiesterase Type 5 Inhibitor, DA-8159 Arch. Pharmacal Res. 2002, 25 ( 6 ) 873-878 10.1007/BF02977007
227. Daugan, A.; Grondin, P.; Ruault, C.; Le Monnier de Gouville, A. C.; Coste, H.; Kirilovsky, J.; Hyafil, F.; Labaudiniere, R. The Discovery of Tadalafil: A Novel and Highly Selective PDE5 Inhibitor. 1:5,6,11,11a-Tetrahydro-1H-Imidazo[1′,5′:1,6]Pyrido[3,4-b]Indole-1,3(2H)-dione Analogues J. Med. Chem. 2003, 46 ( 21 ) 4525-4532 10.1021/jm030056e
228. Haning, H.; Niewohner, U.; Schenke, T.; Es-Sayed, M.; Schmidt, G.; Lampe, T.; Bischoff, E. Imidazo[5,1-f]Triazin-4(3H)-ones, a New Class of Potent PDE 5 Inhibitors Bioorg. Med. Chem. Lett. 2002, 12 ( 6 ) 865-868 10.1016/S0960-894X(02)00030-6
229. Aquilano, K.; Baldelli, S.; Ciriolo, M. R. Nuclear Recruitment of Neuronal Nitric-Oxide Synthase by Alpha-Syntrophin Is Crucial for the Induction of Mitochondrial Biogenesis J. Biol. Chem. 2014, 289 ( 1 ) 365-378 10.1074/jbc.M113.506733
230. Haas, B.; Mayer, P.; Jennissen, K.; Scholz, D.; Berriel Diaz, M.; Bloch, W.; Herzig, S.; Fassler, R.; Pfeifer, A. Protein Kinase G Controls Brown Fat Cell Differentiation and Mitochondrial Biogenesis Sci. Signaling 2009, 2 ( 99 ) ra78 10.1126/scisignal.2000511
231. Kerwin, J. F., Jr.; Lancaster, J. R., Jr.; Feldman, P. L. Nitric Oxide: A New Paradigm for Second Messengers J. Med. Chem. 1995, 38 ( 22 ) 4343-4362 10.1021/jm00022a001
232. Miller, M. R.; Megson, I. L. Recent Developments in Nitric Oxide Donor Drugs Br. J. Pharmacol. 2007, 151 ( 3 ) 305-321 10.1038/sj.bjp.0707224
233. Ashmore, T.; Roberts, L. D.; Morash, A. J.; Kotwica, A. O.; Finnerty, J.; West, J. A.; Murfitt, S. A.; Fernandez, B. O.; Branco, C.; Cowburn, A. S.; Clarke, K.; Johnson, R. S.; Feelisch, M.; Griffin, J. L.; Murray, A. J. Nitrate Enhances Skeletal Muscle Fatty Acid Oxidation via a Nitric Oxide-cGMP-PPAR-Mediated Mechanism BMC Biol. 2015, 13, 110 10.1186/s12915-015-0221-6
234. Dam, A. D.; Mitchell, A. S.; Quadrilatero, J. Induction of Mitochondrial Biogenesis Protects against Caspase-Dependent and Caspase-Independent Apoptosis in L6Myoblasts Biochim. Biophys. Acta, Mol. Cell Res. 2013, 1833 ( 12 ) 3426-3435 10.1016/j.bbamcr.2013.04.014
235. Puzzo, D.; Vitolo, O.; Trinchese, F.; Jacob, J. P.; Palmeri, A.; Arancio, O. Amyloid-Beta Peptide Inhibits Activation of the Nitric Oxide/cGMP/cAMP-Responsive Element-Binding Protein Pathway during Hippocampal Synaptic Plasticity J. Neurosci. 2005, 25 ( 29 ) 6887-6897 10.1523/JNEUROSCI.5291-04.2005
236. Schmidt, P. M.; Schramm, M.; Schroder, H.; Wunder, F.; Stasch, J. P. Identification of Residues Crucially Involved in the Binding of the Heme Moiety of Soluble Guanylate Cyclase J. Biol. Chem. 2004, 279 ( 4 ) 3025-3032 10.1074/jbc.M310141200
237. Methner, C.; Buonincontri, G.; Hu, C. H.; Vujic, A.; Kretschmer, A.; Sawiak, S.; Carpenter, A.; Stasch, J. P.; Krieg, T. Riociguat Reduces Infarct Size and Post-Infarct Heart Failure in Mouse Hearts: Insights from MRI/PET Imaging PLoS One 2013, 8 ( 12 ) e83910 10.1371/journal.pone.0083910
238. Vandendriessche, B.; Rogge, E.; Goossens, V.; Vandenabeele, P.; Stasch, J. P.; Brouckaert, P.; Cauwels, A. The Soluble Guanylate Cyclase Activator BAY 58-2667 Protects against Morbidity and Mortality in Endotoxic Shock by Recoupling Organ Systems PLoS One 2013, 8 ( 8 ) e72155 10.1371/journal.pone.0072155
239. Geschka, S.; Kretschmer, A.; Sharkovska, Y.; Evgenov, O. V.; Lawrenz, B.; Hucke, A.; Hocher, B.; Stasch, J. P. Soluble Guanylate Cyclase Stimulation Prevents Fibrotic Tissue Remodeling and Improves Survival in Salt-Sensitive Dahl Rats PLoS One 2011, 6 ( 7 ) e21853 10.1371/journal.pone.0021853
240. Kalk, P.; Godes, M.; Relle, K.; Rothkegel, C.; Hucke, A.; Stasch, J. P.; Hocher, B. NO-Independent Activation of Soluble Guanylate Cyclase Prevents Disease Progression in Rats with 5/6 Nephrectomy Br. J. Pharmacol. 2006, 148 ( 6 ) 853-859 10.1038/sj.bjp.0706792
241. Bonkale, W. L.; Winblad, B.; Ravid, R.; Cowburn, R. F. Reduced Nitric Oxide Responsive Soluble Guanylyl Cyclase Activity in the Superior Temporal Cortex of Patients with Alzheimer’s Disease Neurosci. Lett. 1995, 187 ( 1 ) 5-8 10.1016/0304-3940(95)11323-O
242. Salloum, F. N.; Das, A.; Samidurai, A.; Hoke, N. N.; Chau, V. Q.; Ockaili, R. A.; Stasch, J. P.; Kukreja, R. C. Cinaciguat, a Novel Activator of Soluble Guanylate Cyclase, Protects against Ischemia/Reperfusion Injury: Role of Hydrogen Sulfide Am. J. Physiol. Heart Circ. Physiol. 2012, 302 ( 6 ) H1347-1354 10.1152/ajpheart.00544.2011
243. Terrett, N. K.; Bell, A. S.; Brown, D.; Ellis, P. Sildenafil (VIAGRA(TM)), a Potent and Selective Inhibitor of Type 5 cGMP Phosphodiesterase with Utility for the Treatment of Male Erectile Dysfunction Bioorg. Med. Chem. Lett. 1996, 6 ( 15 ) 1819-1824 10.1016/0960-894X(96)00323-X
244. Daugan, A.; Grondin, P.; Ruault, C.; Le Monnier de Gouville, A. C.; Coste, H.; Linget, J. M.; Kirilovsky, J.; Hyafil, F.; Labaudiniere, R. The Discovery of Tadalafil: a Novel and Highly Selective PDE5 Inhibitor. 2:2,3,6,7,12,12a-Hexahydropyrazino[1′,2′:1,6]Pyrido[3,4-b]Indole-1,4-dione Analogues J. Med. Chem. 2003, 46 ( 21 ) 4533-4542 10.1021/jm0300577
245. Weeks, J. L.; Zoraghi, R.; Beasley, A.; Sekhar, K. R.; Francis, S. H.; Corbin, J. D. High Biochemical Selectivity of Tadalafil, Sildenafil and Vardenafil for Human Phosphodiesterase 5A1 (PDE5) over PDE11A4 Suggests the Absence of PDE11A4 Cross-Reaction in Patients Int. J. Impotence Res. 2005, 17 ( 1 ) 5-9 10.1038/sj.ijir.3901283
246. Desouza, C.; Parulkar, A.; Lumpkin, D.; Akers, D.; Fonseca, V. A. Acute and Prolonged Effects of Sildenafil on Brachial Artery Flow-Mediated Dilatation in Type 2 Diabetes Diabetes Care 2002, 25 ( 8 ) 1336-1339 10.2337/diacare.25.8.1336
247. Aversa, A.; Vitale, C.; Volterrani, M.; Fabbri, A.; Spera, G.; Fini, M.; Rosano, G. M. Chronic Administration of Sildenafil Improves Markers of Endothelial Function in Men with Type 2 Diabetes Diabet. Med. 2008, 25 ( 1 ) 37-44 10.1111/j.1464-5491.2007.02298.x
248. Fu, L.; Li, F.; Bruckbauer, A.; Cao, Q.; Cui, X.; Wu, R.; Shi, H.; Xue, B.; Zemel, M. B. Interaction Between Leucine and Phosphodiesterase 5 Inhibition in Modulating Insulin Sensitivity and Lipid Metabolism Diabetes, Metab. Syndr. Obes.: Targets Ther. 2015, 8, 227-239 10.2147/DMSO.S82338
249. Grover-Paez, F.; Villegas Rivera, G.; Guillen Ortiz, R. Sildenafil Citrate Diminishes Microalbuminuria and the Percentage of A1c in Male Patients with Type 2 Diabetes Diabetes Res. Clin. Pract. 2007, 78 ( 1 ) 136-140 10.1016/j.diabres.2007.02.006
250. De Toni, L.; Strapazzon, G.; Gianesello, L.; Caretta, N.; Pilon, C.; Bruttocao, A.; Foresta, C. Effects of Type 5-Phosphodiesterase Inhibition on Energy Metabolism and Mitochondrial Biogenesis in Human Adipose Tissue Ex Vivo J. Endocrinol. Invest. 2011, 34 ( 10 ) 738-741 10.1007/BF03346724
251. Koka, S.; Aluri, H. S.; Xi, L.; Lesnefsky, E. J.; Kukreja, R. C. Chronic Inhibition of Phosphodiesterase 5 with Tadalafil Attenuates Mitochondrial Dysfunction in Type 2 Diabetic Hearts: Potential Role of NO/SIRT1/PGC-1alpha Signaling Am. J. Physiol. Heart Circ. Physiol. 2014, 306 ( 11 ) H1558-1568 10.1152/ajpheart.00865.2013
252. Koka, S.; Xi, L.; Kukreja, R. C. Chronic Treatment with Long Acting Phosphodiesterase-5 Inhibitor Tadalafil Alters Proteomic Changes Associated with Cytoskeletal Rearrangement and Redox Regulation in Type 2 Diabetic Hearts Basic Res. Cardiol. 2012, 107 ( 2 ) 249 10.1007/s00395-012-0249-5
253. Sesti, C.; Florio, V.; Johnson, E. G.; Kloner, R. A. The Phosphodiesterase-5 Inhibitor Tadalafil Reduces Myocardial Infarct Size Int. J. Impotence Res. 2007, 19 ( 1 ) 55-61 10.1038/sj.ijir.3901497
254. Das, A.; Xi, L.; Kukreja, R. C. Phosphodiesterase-5 Inhibitor Sildenafil Preconditions Adult Cardiac Myocytes against Necrosis and Apoptosis. Essential Role of Nitric Oxide Signaling J. Biol. Chem. 2005, 280 ( 13 ) 12944-12955 10.1074/jbc.M404706200
255. Ockaili, R.; Salloum, F.; Hawkins, J.; Kukreja, R. C. Sildenafil (Viagra) Induces Powerful Cardioprotective Effect via Opening of Mitochondrial K(ATP) Channels in Rabbits Am. J. Physiol. Heart Circ. Physiol. 2002, 283 ( 3 ) H1263-1269 10.1152/ajpheart.00324.2002
256. Salloum, F. N.; Chau, V. Q.; Hoke, N. N.; Kukreja, R. C. Tadalafil Prevents Acute Heart Failure with Reduced Ejection Fraction in Mice Cardiovasc. Drugs Ther. 2014, 28 ( 6 ) 493-500 10.1007/s10557-014-6559-0
257. Fisher, P. W.; Salloum, F.; Das, A.; Hyder, H.; Kukreja, R. C. Phosphodiesterase-5 Inhibition with Sildenafil Attenuates Cardiomyocyte Apoptosis and Left Ventricular Dysfunction in a Chronic Model of Doxorubicin Cardiotoxicity Circulation 2005, 111 ( 13 ) 1601-1610 10.1161/01.CIR.0000160359.49478.C2
258. Kim, K. H.; Kim, Y. J.; Ohn, J. H.; Yang, J.; Lee, S. E.; Lee, S. W.; Kim, H. K.; Seo, J. W.; Sohn, D. W. Long-Term Effects of Sildenafil in a Rat Model of Chronic Mitral Regurgitation: Benefits of Ventricular Remodeling and Exercise Capacity Circulation 2012, 125 ( 11 ) 1390-1401 10.1161/CIRCULATIONAHA.111.065300
259. Sheng, B.; Wang, X.; Su, B.; Lee, H. G.; Casadesus, G.; Perry, G.; Zhu, X. Impaired Mitochondrial Biogenesis Contributes to Mitochondrial Dysfunction in Alzheimer’s Disease J. Neurochem. 2012, 120 ( 3 ) 419-429 10.1111/j.1471-4159.2011.07581.x
260. DeMarch, Z.; Giampa, C.; Patassini, S.; Martorana, A.; Bernardi, G.; Fusco, F. R. Beneficial Effects of Rolipram in a Quinolinic Acid Model of Striatal Excitotoxicity Neurobiol. Dis. 2007, 25 ( 2 ) 266-273 10.1016/j.nbd.2006.09.006
261. Liu, Z.; Liu, Y.; Gao, R.; Li, H.; Dunn, T.; Wu, P.; Smith, R. G.; Sarkar, P. S.; Fang, X. Ethanol Suppresses PGC-1alpha Expression by Interfering with the cAMP-CREB Pathway in Neuronal Cells PLoS One 2014, 9 ( 8 ) e104247 10.1371/journal.pone.0104247
262. Schwabe, U.; Miyake, M.; Ohga, Y.; Daly, J. W. 4-(3-Cyclopentyloxy-4-Methoxyphenyl)-2-Pyrrolidone (ZK 62711): A Potent Inhibitor of Adenosine Cyclic 3′,5′-Monophosphate Phosphodiesterases in Homogenates and Tissue Slices from Rat Brain Mol. Pharmacol. 1976, 12 ( 6 ) 900-910
263. Dawson, D. L.; Cutler, B. S.; Meissner, M. H.; Strandness, D. E., Jr. Cilostazol Has Beneficial Effects in Treatment of Intermittent Claudication: Results from a Multicenter, Randomized, Prospective, Double-Blind Trial Circulation 1998, 98 ( 7 ) 678-686 10.1161/01.CIR.98.7.678
264. Kodimuthali, A.; Jabaris, S. S.; Pal, M. Recent Advances on Phosphodiesterase 4 Inhibitors for the Treatment of Asthma and Chronic Obstructive Pulmonary Disease J. Med. Chem. 2008, 51 ( 18 ) 5471-5489 10.1021/jm800582j
265. Roma, G.; Di Braccio, M.; Grossi, G.; Piras, D.; Leoncini, G.; Bruzzese, D.; Signorello, M. G.; Fossa, P.; Mosti, L. Synthesis and In Vitro Antiplatelet Activity of New 4-(1-Piperazinyl)Coumarin Derivatives. Human Platelet Phosphodiesterase 3 Inhibitory Properties of the Two Most Effective Compounds Described and Molecular Modeling Study on their Interactions with Phosphodiesterase 3A Catalytic Site J. Med. Chem. 2007, 50 ( 12 ) 2886-2895 10.1021/jm0611511
266. Zuo, L.; Li, Q.; Sun, B.; Xu, Z.; Ge, Z. Cilostazol Promotes Mitochondrial Biogenesis in Human Umbilical Vein Endothelial Cells through Activating the Expression of PGC-1alpha Biochem. Biophys. Res. Commun. 2013, 433 ( 1 ) 52-57 10.1016/j.bbrc.2013.02.068
267. DeMarch, Z.; Giampa, C.; Patassini, S.; Bernardi, G.; Fusco, F. R. Beneficial Effects of Rolipram in the R6/2 Mouse Model of Huntington’s Disease Neurobiol. Dis. 2008, 30 ( 3 ) 375-387 10.1016/j.nbd.2008.02.010
268. Dragicevic, N.; Delic, V.; Cao, C.; Copes, N.; Lin, X.; Mamcarz, M.; Wang, L.; Arendash, G. W.; Bradshaw, P. C. Caffeine Increases Mitochondrial Function and Blocks Melatonin Signaling to Mitochondria in Alzheimer’s Mice and Cells Neuropharmacology 2012, 63 ( 8 ) 1368-1379 10.1016/j.neuropharm.2012.08.018
269. Gong, B.; Vitolo, O. V.; Trinchese, F.; Liu, S.; Shelanski, M.; Arancio, O. Persistent Improvement in Synaptic and Cognitive Functions in an Alzheimer Mouse Model after Rolipram Treatment J. Clin. Invest. 2004, 114 ( 11 ) 1624-1634 10.1172/JCI22831
270. Choi, J. M.; Shin, H. K.; Kim, K. Y.; Lee, J. H.; Hong, K. W. Neuroprotective Effect of Cilostazol against Focal Cerebral Ischemia via Antiapoptotic Action in Rats J. Pharmacol. Exp. Ther. 2002, 300 ( 3 ) 787-793 10.1124/jpet.300.3.787
271. Lee, J. H.; Park, S. Y.; Shin, Y. W.; Hong, K. W.; Kim, C. D.; Sung, S. M.; Kim, K. Y.; Lee, W. S. Neuroprotection by Cilostazol, a Phosphodiesterase type 3 Inhibitor, against Apoptotic White Matter Changes in Rat after Chronic Cerebral Hypoperfusion Brain Res. 2006, 1082 ( 1 ) 182-191 10.1016/j.brainres.2006.01.088
272. Lee, H. R.; Shin, H. K.; Park, S. Y.; Kim, H. Y.; Lee, W. S.; Rhim, B. Y.; Hong, K. W.; Kim, C. D. Cilostazol Suppresses Beta-Amyloid Production by Activating a Disintegrin and Metalloproteinase 10 via the Upregulation of SIRT1-Coupled Retinoic Acid Receptor-Beta J. Neurosci. Res. 2014, 92 ( 11 ) 1581-1590 10.1002/jnr.23421
273. Taguchi, A.; Takata, Y.; Ihara, M.; Kasahara, Y.; Tsuji, M.; Nishino, M.; Stern, D.; Okada, M. Cilostazol Improves Cognitive Function in Patients with Mild Cognitive Impairment: A Retrospective Analysis Psychogeriatrics 2013, 13 ( 3 ) 164-169 10.1111/psyg.12021
274. Sanada, F.; Kanbara, Y.; Taniyama, Y.; Otsu, R.; Carracedo, M.; Ikeda-Iwabu, Y.; Muratsu, J.; Sugimoto, K.; Yamamoto, K.; Rakugi, H.; Morishita, R. Induction of Angiogenesis by a Type III Phosphodiesterase Inhibitor, Cilostazol, through Activation of Peroxisome Proliferator-Activated Receptor-Gamma and cAMP Pathways in Vascular Cells Arterioscler., Thromb., Vasc. Biol. 2016, 36 ( 3 ) 545-552 10.1161/ATVBAHA.115.307011
275. Biscetti, F.; Pecorini, G.; Arena, V.; Stigliano, E.; Angelini, F.; Ghirlanda, G.; Ferraccioli, G.; Flex, A. Cilostazol Improves the Response to Ischemia in Diabetic Mice by a Mechanism Dependent on PPARgamma Mol. Cell. Endocrinol. 2013, 381 ( 1-2 ) 80-87 10.1016/j.mce.2013.07.011
276. Wang, F.; Gao, L.; Gong, B.; Hu, J.; Li, M.; Guan, Q.; Zhao, J. Tissue-Specific Expression of PPAR mRNAs in Diabetic Rats and Divergent Effects of Cilostazol Can. J. Physiol. Pharmacol. 2008, 86 ( 7 ) 465-471 10.1139/Y08-043
277. Chattipakorn, S. C.; Thummasorn, S.; Sanit, J.; Chattipakorn, N. Phosphodiesterase-3 Inhibitor (Cilostazol) Attenuates Oxidative Stress-Induced Mitochondrial Dysfunction in the Heart J. Geriatr. Cardiol. 2014, 11 ( 2 ) 151-157 10.3969/j.issn.1671-5411.2014.02.014
278. Ye, Y.; Qian, J.; Castillo, A. C.; Ling, S.; Ye, H.; Perez-Polo, J. R.; Bajaj, M.; Birnbaum, Y. Phosphodiesterase-3 Inhibition Augments the Myocardial Infarct Size-Limiting Effects of Exenatide in Mice with Type 2 Diabetes Am. J. Physiol. Heart Circ. Physiol. 2013, 304 ( 1 ) H131-141 10.1152/ajpheart.00609.2012
279. Birnbaum, Y.; Castillo, A. C.; Qian, J.; Ling, S.; Ye, H.; Perez-Polo, J. R.; Bajaj, M.; Ye, Y. Phosphodiesterase III Inhibition Increases cAMP Levels and Augments the Infarct Size Limiting Effect of a DPP-4 Inhibitor in Mice with Type-2 Diabetes Mellitus Cardiovasc. Drugs Ther. 2012, 26 ( 6 ) 445-456 10.1007/s10557-012-6409-x
280. Lee, W. C.; Chen, H. C.; Wang, C. Y.; Lin, P. Y.; Ou, T. T.; Chen, C. C.; Wen, M. C.; Wang, J.; Lee, H. J. Cilostazol Ameliorates Nephropathy in Type 1 Diabetic Rats Involving Improvement in Oxidative Stress and Regulation of TGF-Beta and NF-kappaB Biosci., Biotechnol., Biochem. 2010, 74 ( 7 ) 1355-1361 10.1271/bbb.90938
281. Jiao, X. M.; Jiao, X. J.; Zhang, X. G.; Xu, X. P.; Wu, J. X.; Yao, L.; Zhao, J.; Lu, X. F. Cilostazol Reduces Microalbuminuria in Type 2 Diabetic Nephropathy Chin. Med. J. (Engl.) 2013, 126 ( 22 ) 4395-4396
282. Shinoda-Tagawa, T.; Yamasaki, Y.; Yoshida, S.; Kajimoto, Y.; Tsujino, T.; Hakui, N.; Matsumoto, M.; Hori, M. A Phosphodiesterase Inhibitor, Cilostazol, Prevents the Onset of Silent Brain Infarction in Japanese Subjects with Type II Diabetes Diabetologia 2002, 45 ( 2 ) 188-194 10.1007/s00125-001-0740-2
283. Joe, Y.; Zheng, M.; Kim, H. J.; Uddin, M. J.; Kim, S. K.; Chen, Y.; Park, J.; Cho, G. J.; Ryter, S. W.; Chung, H. T. Cilostazol Attenuates Murine Hepatic Ischemia and Reperfusion Injury via Heme Oxygenase-Dependent Activation of Mitochondrial Biogenesis Am. J. Physiol. Gastrointest. Liver Physiol. 2015, 309 ( 1 ) G21-29 10.1152/ajpgi.00307.2014
284. Zhang, L.; Seitz, L. C.; Abramczyk, A. M.; Chan, C. Synergistic Effect of cAMP and Palmitate in Promoting Altered Mitochondrial Function and Cell Death in HepG2 Cells Exp. Cell Res. 2010, 316 ( 5 ) 716-727 10.1016/j.yexcr.2009.12.008
285. Whitaker, R. M.; Wills, L. P.; Stallons, L. J.; Schnellmann, R. G. cGMP-Selective Phosphodiesterase Inhibitors Stimulate Mitochondrial Biogenesis and Promote Recovery from Acute Kidney Injury J. Pharmacol. Exp. Ther. 2013, 347 ( 3 ) 626-634 10.1124/jpet.113.208017
286. Rankovic, Z.; Brust, T. F.; Bohn, L. M. Biased Agonism: An Emerging Paradigm in GPCR Drug Discovery Bioorg. Med. Chem. Lett. 2016, 26 ( 2 ) 241-250 10.1016/j.bmcl.2015.12.024
287. Pang, J.; Xu, X.; Getman, M. R.; Shi, X.; Belmonte, S. L.; Michaloski, H.; Mohan, A.; Blaxall, B. C.; Berk, B. C. G Protein Coupled Receptor Kinase 2 Interacting Protein 1 (GIT1) Is a Novel Regulator of Mitochondrial Biogenesis in Heart J. Mol. Cell. Cardiol. 2011, 51 ( 5 ) 769-776 10.1016/j.yjmcc.2011.06.020
288. Liu, S.; Premont, R. T.; Rockey, D. C. G-Protein-Coupled Receptor Kinase Interactor-1 (GIT1) Is a New Endothelial Nitric-Oxide Synthase (eNOS) Interactor with Functional Effects on Vascular Homeostasis J. Biol. Chem. 2012, 287 ( 15 ) 12309-12320 10.1074/jbc.M111.320465
289. Lin, L. S.; Lanza, T. J., Jr.; Jewell, J. P.; Liu, P.; Shah, S. K.; Qi, H.; Tong, X.; Wang, J.; Xu, S. S.; Fong, T. M.; Shen, C. P.; Lao, J.; Xiao, J. C.; Shearman, L. P.; Stribling, D. S.; Rosko, K.; Strack, A.; Marsh, D. J.; Feng, Y.; Kumar, S.; Samuel, K.; Yin, W.; Van der Ploeg, L. H.; Goulet, M. T.; Hagmann, W. K. Discovery of N-[(1S,2S)-3-(4-Chlorophenyl)-2-(3-Cyanophenyl)-1-Methylpropyl]-2-Methyl-2-{[5-(Trifluoromethyl)Pyridin-2-yl]oxy}Propanamide (MK-0364), a Novel, Acyclic Cannabinoid-1 Receptor Inverse Agonist for the Treatment of Obesity J. Med. Chem. 2006, 49 ( 26 ) 7584-7587 10.1021/jm060996+
290. Rinaldi-Carmona, M.; Barth, F.; Héaulme, M.; Shire, D.; Calandra, B.; Congy, C.; Martinez, S.; Maruani, J.; Néliat, G.; Caput, D.; Ferrara, P.; Soubrié, P.; Brelière, J. C.; Le Fur, G. SR141716A, a Potent and Selective Antagonist of the Brain Cannabinoid Receptor FEBS Lett. 1994, 350 ( 2-3 ) 240-244 10.1016/0014-5793(94)00773-X
291. Lin, L. S.; Ha, S.; Ball, R. G.; Tsou, N. N.; Castonguay, L. A.; Doss, G. A.; Fong, T. M.; Shen, C. P.; Xiao, J. C.; Goulet, M. T.; Hagmann, W. K. Conformational Analysis and Receptor Docking of N-[(1S,2S)-3-(4-Chlorophenyl)-2-(3-Cyanophenyl)-1-Methylpropyl]-2-Methyl-2-{[5-(Trifluoromethyl)Pyridin-2-yl]oxy}Propanamide (Taranabant, MK-0364), a Novel, Acyclic Cannabinoid-1 Receptor Inverse Agonist J. Med. Chem. 2008, 51 ( 7 ) 2108-2114 10.1021/jm7014974
292. Tedesco, L.; Valerio, A.; Cervino, C.; Cardile, A.; Pagano, C.; Vettor, R.; Pasquali, R.; Carruba, M. O.; Marsicano, G.; Lutz, B.; Pagotto, U.; Nisoli, E. Cannabinoid Type 1 Receptor Blockade Promotes Mitochondrial Biogenesis through Endothelial Nitric Oxide Synthase Expression in White Adipocytes Diabetes 2008, 57 ( 8 ) 2028-2036 10.2337/db07-1623
293. Liu, Y. L.; Connoley, I. P.; Wilson, C. A.; Stock, M. J. Effects of the Cannabinoid CB1 Receptor Antagonist SR141716 on Oxygen Consumption and Soleus Muscle Glucose Uptake in Lep(ob)/Lep(ob) Mice Int. J. Obes. 2005, 29 ( 2 ) 183-187 10.1038/sj.ijo.0802847
294. Flamment, M.; Gueguen, N.; Wetterwald, C.; Simard, G.; Malthiery, Y.; Ducluzeau, P. H. Effects of the Cannabinoid CB1 Antagonist Rimonabant on Hepatic Mitochondrial Function in Rats Fed a High-Fat Diet Am. J. Physiol. Endocrinol. Metab. 2009, 297 ( 5 ) E1162-1170 10.1152/ajpendo.00169.2009
295. Topol, E. J.; Bousser, M. G.; Fox, K. A.; Creager, M. A.; Despres, J. P.; Easton, J. D.; Hamm, C. W.; Montalescot, G.; Steg, P. G.; Pearson, T. A.; Cohen, E.; Gaudin, C.; Job, B.; Murphy, J. H.; Bhatt, D. L.; Investigators, C. Rimonabant for Prevention of Cardiovascular Events (CRESCENDO): A Randomised, Multicentre, Placebo-Controlled Trial Lancet 2010, 376 ( 9740 ) 517-523 10.1016/S0140-6736(10)60935-X
296. Addy, C.; Wright, H.; Van Laere, K.; Gantz, I.; Erondu, N.; Musser, B. J.; Lu, K.; Yuan, J.; Sanabria-Bohorquez, S. M.; Stoch, A.; Stevens, C.; Fong, T. M.; De Lepeleire, I.; Cilissen, C.; Cote, J.; Rosko, K.; Gendrano, I. N., 3rd; Nguyen, A. M.; Gumbiner, B.; Rothenberg, P.; de Hoon, J.; Bormans, G.; Depre, M.; Eng, W. S.; Ravussin, E.; Klein, S.; Blundell, J.; Herman, G. A.; Burns, H. D.; Hargreaves, R. J.; Wagner, J.; Gottesdiener, K.; Amatruda, J. M.; Heymsfield, S. B. The Acyclic CB1R Inverse Agonist Taranabant Mediates Weight Loss by Increasing Energy Expenditure and Decreasing Caloric Intake Cell Metab. 2008, 7 ( 1 ) 68-78 10.1016/j.cmet.2007.11.012
297. Rapport, M. M.; Green, A. A.; Page, I. H. Serum Vasoconstrictor, Serotonin; Isolation and Characterization J. Biol. Chem. 1948, 176 ( 3 ) 1243-1251
298. Ismaiel, A. M.; Titeler, M.; Miller, K. J.; Smith, T. S.; Glennon, R. A. 5-HT1 and 5-HT2 Binding Profiles of the Serotonergic Agents Alpha-Methylserotonin and 2-Methylserotonin J. Med. Chem. 1990, 33 ( 2 ) 755-758 10.1021/jm00164a046
299. Diksic, M.; Nagahiro, S.; Sourkes, T. L.; Yamamoto, Y. L. A New Method to Measure Brain Serotonin Synthesis In Vivo. I. Theory and Basic Data for a Biological Model J. Cereb. Blood Flow Metab. 1990, 10 ( 1 ) 1-12 10.1038/jcbfm.1990.1
300. Glennon, R. A. Discriminative Stimulus Properties of the Serotonergic Agent 1-(2,5-Dimethoxy-4-Iodophenyl)-2-Aminopropane (DOI) Life Sci. 1986, 39 ( 9 ) 825-830 10.1016/0024-3205(86)90461-3
301. Glennon, R. A.; McKenney, J. D.; Lyon, R. A.; Titeler, M. 5-HT1 and 5-HT2 Binding Characteristics of 1-(2,5-Dimethoxy-4-Bromophenyl)-2-Aminopropane Analogues J. Med. Chem. 1986, 29 ( 2 ) 194-199 10.1021/jm00152a005
302. Siuciak, J. A.; Chapin, D. S.; McCarthy, S. A.; Guanowsky, V.; Brown, J.; Chiang, P.; Marala, R.; Patterson, T.; Seymour, P. A.; Swick, A.; Iredale, P. A. CP-809,101, a Selective 5-HT2C Agonist, Shows Activity in Animal Models of Antipsychotic Activity Neuropharmacology 2007, 52 ( 2 ) 279-290 10.1016/j.neuropharm.2006.07.024
303. Kennett, G. A.; Wood, M. D.; Bright, F.; Trail, B.; Riley, G.; Holland, V.; Avenell, K. Y.; Stean, T.; Upton, N.; Bromidge, S.; Forbes, I. T.; Brown, A. M.; Middlemiss, D. N.; Blackburn, T. P. SB 242084, a Selective and Brain Penetrant 5-HT2C Receptor Antagonist Neuropharmacology 1997, 36 ( 4-5 ) 609-620 10.1016/S0028-3908(97)00038-5
304. Heifetz, A.; Storer, R. I.; McMurray, G.; James, T.; Morao, I.; Aldeghi, M.; Bodkin, M. J.; Biggin, P. C. Application of an Integrated GPCR SAR-Modeling Platform to Explain the Activation Selectivity of Human 5-HT2C over 5-HT2B ACS Chem. Biol. 2016, 11, 1372 10.1021/acschembio.5b01045
305. Wong, D. T.; Horng, J. S.; Bymaster, F. P.; Hauser, K. L.; Molloy, B. B. A Selective Inhibitor of Serotonin Uptake: Lilly 110140, 3-(p-Trifluoromethylphenoxy)-N-Methyl-3-Phenylpropylamine Life Sci. 1974, 15 ( 3 ) 471-479 10.1016/0024-3205(74)90345-2
306. Andersen, J.; Kristensen, A. S.; Bang-Andersen, B.; Stromgaard, K. Recent Advances in the Understanding of the Interaction of Antidepressant Drugs with Serotonin and Norepinephrine Transporters Chem. Commun. (Cambridge, U. K.) 2009, 25 ) 3677-3692 10.1039/b903035m
307. Henry, L. K.; Field, J. R.; Adkins, E. M.; Parnas, M. L.; Vaughan, R. A.; Zou, M. F.; Newman, A. H.; Blakely, R. D. Tyr-95 and Ile-172 in Transmembrane Segments 1 and 3 of Human Serotonin Transporters Interact to Establish High Affinity Recognition of Antidepressants J. Biol. Chem. 2006, 281 ( 4 ) 2012-2023 10.1074/jbc.M505055200
308. Braz, G. R.; Freitas, C. M.; Nascimento, L.; Pedroza, A. A.; da Silva, A. I.; Lagranha, C. Neonatal SSRI Exposure Improves Mitochondrial Function and Antioxidant Defense in Rat Heart Appl. Physiol., Nutr., Metab. 2016, 41 ( 4 ) 362-369 10.1139/apnm-2015-0494
309. Garrett, S. M.; Whitaker, R. M.; Beeson, C. C.; Schnellmann, R. G. Agonism of the 5-Hydroxytryptamine 1F Receptor Promotes Mitochondrial Biogenesis and Recovery from Acute Kidney Injury J. Pharmacol. Exp. Ther. 2014, 350 ( 2 ) 257-264 10.1124/jpet.114.214700
310. Rasbach, K. A.; Funk, J. A.; Jayavelu, T.; Green, P. T.; Schnellmann, R. G. 5-Hydroxytryptamine Receptor Stimulation of Mitochondrial Biogenesis J. Pharmacol. Exp. Ther. 2010, 332 ( 2 ) 632-639 10.1124/jpet.109.159947
311. Harmon, J. L.; Wills, L. P.; McOmish, C. E.; Demireva, E. Y.; Gingrich, J. A.; Beeson, C. C.; Schnellmann, R. G. 5-HT2 Receptor Regulation of Mitochondrial Genes: Unexpected Pharmacological Effects of Agonists and Antagonists J. Pharmacol. Exp. Ther. 2016, 357 ( 1 ) 1-9 10.1124/jpet.115.228395
312. Sneader, W. The Discovery and Synthesis of Epinephrine Drug News Perspect. 2001, 14 ( 8 ) 491-494 10.1358/dnp.2001.14.8.858417
313. Chapple, C.; Khullar, V.; Nitti, V. W.; Frankel, J.; Herschorn, S.; Kaper, M.; Blauwet, M. B.; Siddiqui, E. Efficacy of the Beta3-Adrenoceptor Agonist Mirabegron for the Treatment of Overactive Bladder by Severity of Incontinence at Baseline: A Post Hoc Analysis of Pooled Data from Three Randomised Phase 3 Trials Eur. Urol. 2015, 67 ( 1 ) 11-14 10.1016/j.eururo.2014.06.052
314. Konzett, H.; Rössler, R. Versuchsanordnung zu Untersuchungen an der Bronchiàlmuskulatur Naunyn-Schmiedeberg's Arch. Pharmacol. 1940, 195 ( 1 ) 71-74 10.1007/BF01861842
315. Muller, T. D.; Lee, S. J.; Jastroch, M.; Kabra, D.; Stemmer, K.; Aichler, M.; Abplanalp, B.; Ananthakrishnan, G.; Bhardwaj, N.; Collins, S.; Divanovic, S.; Endele, M.; Finan, B.; Gao, Y.; Habegger, K. M.; Hembree, J.; Heppner, K. M.; Hofmann, S.; Holland, J.; Kuchler, D.; Kutschke, M.; Krishna, R.; Lehti, M.; Oelkrug, R.; Ottaway, N.; Perez-Tilve, D.; Raver, C.; Walch, A. K.; Schriever, S. C.; Speakman, J.; Tseng, Y. H.; Diaz-Meco, M.; Pfluger, P. T.; Moscat, J.; Tschop, M. H. p62 Links Beta-Adrenergic Input to Mitochondrial Function and Thermogenesis J. Clin. Invest. 2013, 123 ( 1 ) 469-478 10.1172/JCI64209
316. Tuttle, R. R.; Mills, J. Dobutamine: Development of a New Catecholamine to Selectively Increase Cardiac Contractility Circ. Res. 1975, 36 ( 1 ) 185-196 10.1161/01.RES.36.1.185
317. Wang, Y.; Wang, Y.; Yang, D.; Yu, X.; Li, H.; Lv, X.; Lu, D.; Wang, H. Beta(1)-Adrenoceptor Stimulation Promotes LPS-Induced Cardiomyocyte Apoptosis through Activating PKA and Enhancing CaMKII and IkappaBalpha Phosphorylation Crit. Care 2015, 19, 76 10.1186/s13054-015-0820-1
318. Regardh, C. G.; Borg, K. O.; Johansson, R.; Johnsson, G.; Palmer, L. Pharmacokinetic Studies on the Selective Beta1-Receptor Antagonist Metoprolol in Man J. Pharmacokinet. Biopharm. 1974, 2 ( 4 ) 347-364 10.1007/BF01061407
319. Sharma, V.; Dhillon, P.; Parsons, H.; Allard, M. F.; McNeill, J. H. Metoprolol Represses PGC1alpha-Mediated Carnitine Palmitoyltransferase-1B Expression in the Diabetic Heart Eur. J. Pharmacol. 2009, 607 ( 1-3 ) 156-166 10.1016/j.ejphar.2009.02.016
320. Sharma, V.; Dhillon, P.; Wambolt, R.; Parsons, H.; Brownsey, R.; Allard, M. F.; McNeill, J. H. Metoprolol Improves Cardiac Function and Modulates Cardiac Metabolism in the Streptozotocin-Diabetic Rat Am. J. Physiol. Heart Circ. Physiol. 2008, 294 ( 4 ) H1609-1620 10.1152/ajpheart.00949.2007
321. Ida, H. [General Pharmacology of (Alpha RS)-3-Formamido-4-Hydroxy-Alpha-[[[(Alpha RS)-p-Methoxy-Alpha-Methylphenethyl]Amino]Methyl] Benzyl Alcohol Fumarate Dihydrate (BD 40A), a New Bronchodilator Agent (Author’s Transl)] Nippon Yakurigaku Zasshi 1980, 76 ( 7 ) 633-654 10.1254/fpj.76.633
322. Rominger, K. L.; Pollmann, W. [Comparative Pharmacokinetic Studies on Fenoterol-Hydrobromide in Rat, Dog and Man] Arzneimittelforschung. 1972, 22 ( 7 ) 1190-1196
323. Yoshizaki, S.; Manabe, Y.; Tamada, S.; Nakagawa, K.; Tei, S. Isomers of Erythro-5-(1-Hydroxy-2-Isopropylaminobutyl)-8-Hydroxycarbostyril, a New Bronchodilator J. Med. Chem. 1977, 20 ( 8 ) 1103-1104 10.1021/jm00218a024
324. Peterson, Y. K.; Cameron, R. B.; Wills, L. P.; Trager, R. E.; Lindsey, C. C.; Beeson, C. C.; Schnellmann, R. G. Beta2-Adrenoceptor Agonists in the Regulation of Mitochondrial Biogenesis Bioorg. Med. Chem. Lett. 2013, 23 ( 19 ) 5376-5381 10.1016/j.bmcl.2013.07.052
325. Wills, L. P.; Trager, R. E.; Beeson, G. C.; Lindsey, C. C.; Peterson, Y. K.; Beeson, C. C.; Schnellmann, R. G. The Beta2-Adrenoceptor Agonist Formoterol Stimulates Mitochondrial Biogenesis J. Pharmacol. Exp. Ther. 2012, 342 ( 1 ) 106-118 10.1124/jpet.112.191528
326. Jesinkey, S. R.; Funk, J. A.; Stallons, L. J.; Wills, L. P.; Megyesi, J. K.; Beeson, C. C.; Schnellmann, R. G. Formoterol Restores Mitochondrial and Renal Function after Ischemia-Reperfusion Injury J. Am. Soc. Nephrol. 2014, 25 ( 6 ) 1157-1162 10.1681/ASN.2013090952
327. Nolte, D.; Laumen, F. [Pulmonary Function Tests Using the Broncholytic Agent NAB 365] Med. Monatsschr. 1972, 26 ( 7 ) 325-328
328. Lands, A. M.; Luduena, F. P.; Hoppe, J. O.; Oyen, I. H. The Pharmacologic Actions of the Bronchodilator Drug, Isoetharine J. Am. Pharm. Assoc., Sci. Ed. 1958, 47 ( 10 ) 744-748 10.1002/jps.3030471017
329. Jesinkey, S. R.; Korrapati, M. C.; Rasbach, K. A.; Beeson, C. C.; Schnellmann, R. G. Atomoxetine Prevents Dexamethasone-Induced Skeletal Muscle Atrophy in Mice J. Pharmacol. Exp. Ther. 2014, 351 ( 3 ) 663-673 10.1124/jpet.114.217380
330. Ott, I. M.; Alter, M. L.; von Websky, K.; Kretschmer, A.; Tsuprykov, O.; Sharkovska, Y.; Krause-Relle, K.; Raila, J.; Henze, A.; Stasch, J. P.; Hocher, B. Effects of Stimulation of Soluble Guanylate Cyclase on Diabetic Nephropathy in Diabetic eNOS Knockout Mice on Top of Angiotensin II Receptor Blockade PLoS One 2012, 7 ( 8 ) e42623 10.1371/journal.pone.0042623
331. Wassermann, A. M.; Lounkine, E.; Hoepfner, D.; Le Goff, G.; King, F. J.; Studer, C.; Peltier, J. M.; Grippo, M. L.; Prindle, V.; Tao, J.; Schuffenhauer, A.; Wallace, I. M.; Chen, S.; Krastel, P.; Cobos-Correa, A.; Parker, C. N.; Davies, J. W.; Glick, M. Dark Chemical Matter as a Promising Starting Point for Drug Lead Discovery Nat. Chem. Biol. 2015, 11 ( 12 ) 958-966 10.1038/nchembio.1936