Mitochondrial dysfunction and targeted drugs: A focus on diabetes

Current Pharmaceutical Design

Volumn 17, Issue 20, 2011, Pages 1986-2001

  Victor, Victor M ^a,b   Rocha, Milagros ^a   Bañuls, Celia ^a   Bellod, Lorena ^a   Hernandez Mijares, Antonio ^a,b  

^a HOSPITAL UNIVERSITARIO DR PESET   (Spain)

^b UNIVERSITY OF VALENCIA   (Spain)

Author keywords

Diabetes; Mitochondria; Oxidative stress; Reactive oxygen species

Indexed keywords

2 METHOXYESTRADIOL; ALPHA TOCOPHEROL; ALPHA TOCOPHEROL SUCCINATE; ANNONACEOUS ACETOGENINS EXTRACT; ANTIMYCIN A1; ANTIOXIDANT; ASCORBIC ACID; BENZODIAZEPINE DERIVATIVE; BZ 423; DIINDOLYL METHANE; ELESCLOMOL; GRAMICIDIN S; INDOLE DERIVATIVE; MACROLIDE; MITOCHONDRIAL PERMEABILITY TRANSITION PORE; MITOPEROXIDASE; MITOQ; MYXOTHIAZOL; N SEC BUTYL 1 (2 CHLOROPHENYL) N METHYL 3 ISOQUINOLINECARBOXAMIDE; OLIGOMYCIN; PLANT EXTRACT; PLASTOQUINONE; POLYPEPTIDE; REACTIVE NITROGEN SPECIES; REACTIVE OXYGEN METABOLITE; RESVERATROL; ROTENONE; SS PEPTIDE; UNCLASSIFIED DRUG;

ARTHRITIS; AUTOIMMUNE DISEASE; CANCER RISK; DIABETES MELLITUS; DISORDERS OF MITOCHONDRIAL FUNCTIONS; DRUG TARGETING; ELECTRON TRANSPORT; HEART DISEASE; HUMAN; INFLAMMATION; LUPUS VULGARIS; MITOCHONDRIAL TOXICITY; NEOPLASM; NONHUMAN; OXIDATIVE STRESS; PARKINSON DISEASE; PRIORITY JOURNAL; PSORIASIS; REVIEW;

ANTIOXIDANTS; CLINICAL TRIALS AS TOPIC; DIABETES MELLITUS; HUMANS; MITOCHONDRIA; MOLECULAR TARGETED THERAPY; OXIDATIVE STRESS; REACTIVE OXYGEN SPECIES;

EID: 80052206063     PISSN: 13816128     EISSN: 18734286     Source Type: Journal    
DOI: 10.2174/138161211796904722     Document Type: Review

References (189)

1. Gutteridge JM, Mitchell J. Redox imbalance in critical ill. Br Med Bull 1999; 55: 49-75.
2. Gutteridge JM. Lipid peroxidation and antioxidants as biomarkers of tissue damage. Clin Chem 1995; 41: 1819-28.
3. Schachinger V, Britten MB, Zeiher AM. Prognostic impact of coronary vasodilator dysfunction on adverse long-term outcome of coronary heart disease. Circulation 2000; 101: 1899-906.
4. Brown GC, Borutaite V. There is no evidence that mitochondria are the main source of reactive oxygen species in mammalian cells. Mitochondrion. 2011 Feb 15.
5. Kowaltowski, AJ, Vercesi AE. Mitochondrial damage induced by conditions of oxidative stress. Free Radic Biol Med 1999; 26: 463-71.
6. Victor VM, Rocha M, De la Fuente M. N-acetylcysteine protects mice from lethal endotoxemia by regulating the redox state of immune cells. Free Radic Res 2003; 37: 919-29.
7. Victor VM, Rocha, M, De la Fuente M. Immune cells: free radicals and antioxidants in sepsis. Int Immunopharmacol 2004; 4: 327-47.
8. Victor VM, Rocha M, Esplugues, JV, De la Fuente M. Role of free radicals in sepsis: antioxidant therapy. Curr Pharm Des 2005; 11: 3141-58.
9. Kagan, VE, Serbinova EA, Stoyanovsky DA, Khwaja S, Packer L. Assay of ubiquinones and ubiquinols as antioxidants. Methods Enzymol 1994; 234: 343-54.
10. Sheu SS, Nauduri D, Anders MW. Targeting antioxidants to mitochondria: a new therapeutic direction. Biochim Biophys Acta 2006; 1762: 256-65.
11. Victor VM, Rocha M. Targeting antioxidants to mitochondria: a potential new therapeutic strategy for cardiovascular diseases. Curr Pharm Des 2007; 13: 845-63.
12. Victor VM, Apostolova N, Herance R, Hernandez-Mijares A, Rocha M. Oxidative stress and mitochondrial dysfunction in atherosclerosis: mitochondria-targeted antioxidants as potential therapy. Curr Med Chem 2009; 16: 4654-67.
13. Cadenas E, Boveris A, Ragan CI, Stoppani AO. Production of superoxide radicals and hydrogen peroxide by NADH-ubiquinone reductase and ubiquinol-cytochrome c reductase from beef-heart mitochondria. Arch Biochem Biophys 1977; 180: 248-57.
14. Boveris A, Oshino N, Chance B. The cellular production of hydrogen peroxide, Biochem J 1972; 128: 617-30.
15. Turrens JF. Mitochondrial formation of reactive oxygen species. J Physiol 2003; 552: 335-44.
16. Sun J, Trumpower BL. Superoxide anion generation by the cytochrome bc1 complex. Arch Biochem Biophys 2003; 198-206.
17. St-Pierre J, Buckingham JA, Roebuck SJ, Brand MD. Topology of superoxide production from different sites in the mitochondrial electron transport chain. J. Biol. Chem 2002; 277: 44784-90.
18. Grivennikova VG, Vinogradov AD. Generation of superoxide by the mitochondrial complex I. Biochim Biophys Acta 2006; 1757: 553-61.
19. Lambert AJ, Buckingham JA, Boysen HM, Brand MD. Diphenyleneiodonium acutely inhibits reactive oxygen species production by mitochondrial complex I during reverse, but not forward electron transport. Biochim Biophys Acta 2008; 1777: 397-403.
20. Kudin AP, Malinska D, Kunz WS. Sites of generation of reactive oxygen species in homogenates of brain tissue determined with the use of respiratory substrates and inhibitors. Biochim Biophys Acta 2008; 1777: 689-95
21. Echtay KS. Mitochondrial uncoupling proteins - what is their physiological role?. Free Radic Biol Med 2007; 43: 1351-71.
22. Okado-Matsumoto A, Fridovich I. Subcellular distribution of superoxide dismutases (SOD) in rat liver: Cu, Zn-SOD in mitochondria. J Biol Chem 2001; 276: 38388-93.
23. O'Brien KM, Dirmeier R, Engle M, Poyton RO Mitochondrial protein oxidation in yeast mutants lacking manganese-(MnSOD) or copper- and zinc-containing superoxide dismutase (CuZnSOD): evidence that MnSOD and CuZnSOD have both unique and overlapping functions in protecting mitochondrial proteins from oxidative damage. J Biol Chem 2004; 279: 51817-27.
24. Boveris A, Cadenas E. cellular sources and steady-state levels of reactive oxygen species, in: LB Clerch, DJ Massaro (Eds), Oxygen, gene expression, and cellular function. New York: Marcel Dekker 1997; pp. 1-25.
25. Satarkov AA, Fiskum G, Chinopoulos C, et al. Mitochondrialα- ketoglutarate dehydrogenase complex generates reactive oxygen species. J Neurosci 2004; 24: 7779-88.
26. Rains JL, Jain SK. Oxidative stress, insulin signaling, and diabetes. Free Radic Biol Med 2011; 50: 567-75.
27. Lassègue B, Griendling KK. NADPH oxidases: functions and pathologies in the vasculature. Arterioscler Thromb Vasc Biol. 2010; 30: 653-61.
28. San Martin A, Du P, Dikalova A, et al. Reactive oxygen speciesselective regulation of aortic inflammatory gene expression in Type 2 diabetes. Am J Physiol Heart Circ Physiol 2007; 292: H2073-82.
29. Ding H, Hashem M, Triggle C. Increased oxidative stress in the streptozotocin-induced diabetic apoE-deficient mouse: changes in expression of NADPH oxidase subunits and eNOS. Eur J Pharmacol 2007; 561: 121-8.
30. Jung O, Schreiber JG, Geiger H, Pedrazzini T, Busse R, Brandes RP. gp91phox-containing NADPH oxidase mediates endothelial dysfunction in renovascular hypertension. Circulation 2004; 109: 1795-801
31. Fujii A, Nakano D, Katsuragi M, et al. Role of gp91phoxcontaining NADPH oxidase in the deoxycorticosterone acetate-saltinduced hypertension. Eur J Pharmacol 2006; 552: 131-4
32. Liu JQ, Zelko IN, Erbynn EM, Sham JS, Folz RJ. Hypoxic pulmonary hypertension: role of superoxide and NADPH oxidase (gp91phox). Am J Physiol Lung Cell Mol Physiol 2006; 290: L2-L10
33. Matsuno K, Yamada H, Iwata K, et al. Nox1 is involved in angiotensin II-mediated hypertension: a study in Nox1-deficient mice. Circulation 2005; 112: 2677-85.
34. Wang HD, Xu S, Johns DG, et al. Role of NADPH oxidase in the vascular hypertrophic and oxidative stress response to angiotensin II in mice. Circ Res 2001; 88: 947-53
35. Yogi A, Mercure C, Touyz J, et al. Renal redox-sensitive signaling, but not blood pressure, is attenuated by Nox1 knockout in angiotensin II-dependent chronic hypertension. Hypertension 2008; 51: 500-6
36. Fialkow L, Wang Y, Downey GP. Reactive oxygen and nitrogen species as signaling molecules regulating neutrophil function. Free Radic Biol Med 2007; 42: 153-64.
37. Huie RE, Padmaja S. The reaction of NO with superoxide. Free Radic Res Commun 1993; 18: 195-9.
38. Rocha M, Victor VM. Targeting antioxidants to mitochondria and cardiovascular diseases: the effects of mitoquinone. Med Sci Monit 2007; 13: 132-45.
39. Rocha M, Apostolova N, Hernandez-Mijares A, Herance R, Victor VM. Oxidative stress and endothelial dysfunction in cardiovascular disease: mitochondria-targeted therapeutics. Curr Med Chem. 2010; 17: 3827-41.
40. Poderoso JJ, Carreras MC, Lisdero C, Riobó N, Schöpfer F, Boveris A. Nitric oxide inhibits electron transfer and increases superoxide radical production in rat heart mitochondria and submitochondrial particles. Arch Biochem Biophys 1996; 328: 85-92.
41. Papadaki M, Tilton RG, Eskin SG, McIntire LV. Nitric oxide production by cultured human aortic smooth muscle cells: stimulation by fluid flow. Am J Physiol. 1998; 274: H616-26.
42. Stocker R, Keaney JF Jr. Role of oxidative modifications in atherosclerosis. Physiol Rev. 2004; 84: 1381-478.
43. Swain JA, Darley-Usmar V, Gutteridge JM. Peroxynitrite releases copper from caeruloplasmin: implications for atherosclerosis. FEBS Lett 1994; 342: 49-52.
44. Zou MH, Ullrich V. Peroxynitrite formed by simultaneous generation of nitric oxide and superoxide selectively inhibits bovine aortic prostacyclin synthase. FEBS Lett. 1996; 382: 101-14.
45. MacMillan-Crow LA, Thompson JA. Tyrosine modifications and inactivation of active site manganese superoxide dismutase mutant (Y34F) by peroxynitrite. Arch Biochem Biophys. 1999; 366: 82-8.
46. Wong PS, Eiserich JP, Reddy S, Lopez CL, Cross CE, van der Vliet A. Inactivation of glutathione S-transferases by nitric oxidederived oxidants: exploring a role for tyrosine nitration. Arch Biochem Biophys. 2001; 394: 216-28.
47. Brandes RP, Kreuzer J. Vascular NADPH oxidases: molecular mechanisms of activation. Cardiovasc Res. 2005; 65: 16-27.
48. Li WG, Miller FJ, Jr., Zhang HJ, Spitz DR, Oberley LW, Weintraub NL. H(2)O(2)-induced O(2) production by a non-phagocytic NAD(P)H oxidase causes oxidant injury. J Biol Chem. 2001; 276: 29251-6.
49. Li WG, Stoll LL, Rice JB, et al. Activation of NAD(P)H oxidase by lipid hydroperoxides: mechanism of oxidant-mediated smooth muscle cytotoxicity. Free Radic Biol Med. 2003; 34: 937-46.
50. Trebak M, Ginnan R, Singer HA, Jourd'heuil D. Interplay between calcium and reactive oxygen/nitrogen species: an essential paradigm for vascular smooth muscle signaling. Antioxid Redox Signal. 2010; 12: 657-74.
51. White MY, Edwards AV, Cordwell, JJ, Van Eyk JE. Mitochondria: a mirror into cellular dysfunction in heart disease. Proteomics Clin Appl 2008; 2: 845-61.
52. Youle RJ, Narendra DP. Mechanisms of mitophagy. Nat Rev Mol Cell Biol 2011; 12: 9-14.
53. DiMauro S, Schon EA. Mitochondrial respiratory-chain diseases. N Engl J Med 2003, 348: 2656-68.
54. Rocha M, Hernandez-Mijares A, Garcia-Malpartida K, Bañuls C, Bellod L, Victor VM. Mitochondria-targeted antioxidant peptides. Curr Pharm Des 2010; 16: 3124-31.
55. Houstek J, Pickova A, Vojtiskova A, Mracek T, Pecina P, Jesina P. Mitochondrial diseases and genetic defects of ATP synthase. Biochim Biophys Acta 2006; 1757: 1400-5.
56. Keane PC, Kurzawa M, Blain PG, Morris CM. Mitochondrial dysfunction in Parkinson's disease. Parkinsons Dis. 2011; 2011: 716-871.
57. Shoffner JM, Wallace DC. Heart disease and mitochondrial DNA mutations. Heart Dis Stroke 1992; 1: 235-41.
58. Pastores GM, Santorelli FM, Shanske S, et al. Leigh syndrome and hypertrophic cardiomyopathy in an infant with a mitochondrial point mutation (T8993G). Am J Med Genet 1994; 50: 265-71.
59. Anan R, Nakagawa M, Miyata M, et al. Cardiac involvement in mitochondrial diseases: a study of 17 patients with mitochondrial DNA defects. Circulation 1995; 91: 955-61.
60. Graf WD, Marín-García J, Gao HG, et al. Autism associated with the mitochondrial DNA G8363A transfer RNA(Lys)mutation. J Child Neurol 2000; 15: 357-61.
61. Matthews PM, Marchington DR, Squier M, Land J, Brown R, Brown GK. Molecular genetic characterization of an X-linked form of Leigh's syndrome. Ann Neurol 1993; 33: 652-5.
62. Bourgeron T, Rustin P, Chretien D, et al. Mutation of a nuclear succinate dehydrogenase gene results in mitochondrial respiratory chain deficiency. Nat Genet 1995; 11: 144-9.
63. Filiano JJ, Goldenthal MJ, Mamourian AC, Hall CC, Marín-García J. Mitochondrial DNA depletion in Leigh syndrome. Pediatr Neurol 2002; 26: 239-42.
64. Brookes PS, Yoon Y, Robotham JL, Anders MW, Sheu SS. Calcium, ATP, and ROS: a mitochondrial love-hate triangle. Am J Physiol Cell Physiol 2004; 287: 817-33.
65. Indo HP, Davidson M, Yen HC, et al. Evidence of ROS generation by mitochondria in cells with impaired electron transport chain and mitochondrial DNA damage. Mitochondrion 2007; 7: 106-18.
66. Stavrovskaya, I.G, Kristal BS. The powerhouse takes control of the cell: is the mitochondrial permeability transition a viable therapeutic target against neuronal dysfunction and death? Free Radic Biol Med 2005; 38: 687-97.
67. Victor, VM, Rocha M, Bañuls C, et al. Mitochondrial complex I impairment in leukocytes from polycystic ovary syndrome patients with insulin resistance. J Clin Endocrinol Metab 2009; 94: 3505-12.
68. Esplugues JV, Rocha M, Nuñez C, et al. Complex I dysfunction and tolerance to nitroglycerin: an approach based on mitochondrialtargeted antioxidants. Circ Res 2006; 99: 1067-75.
69. Levy JR, Gavin 3rd JR, Sowers JR. Diabetes mellitus: a disease of abnormal cellular calcium metabolism?. Am J Med 1994; 96 260-73.
70. Fedirko NV, Kruglikov IA, Kopach OV, Vats JA, Kostyuk PG, Voitenko NV. Changes in functioning of rat submandibular salivary gland under streptozotocin-induced diabetes are associated with alterations of Ca2+ signaling and Ca2+ transporting pumps. Biochim Biophys Acta 2006; 1762: 294-303.
71. Di Lisa F, Bernardi P. Mitochondrial function and myocardial aging. A critical analysis of the role of permeability transition. Cardiovasc Res 2005; 66: 222-32.
72. Yakes FM, Van Houten B. Mitochondrial DNA damage is more extensive and persists longer than nuclear DNA damage in human cells following oxidative stress. Proc Natl Acad Sci USA 1997; 94: 514-9.
73. Wu YT, Wu SB, Lee WY, Wei YH. Mitochondrial respiratory dysfunction-elicited oxidative stress and posttranslational protein modification in mitochondrial diseases. Ann N Y Acad Sci 2010; 1201: 147-56.
74. Ramachandran A, Moellering DR, Ceaser E, Shiva S, Xu J, Darley-Usmar V. Inhibition of mitochondrial protein synthesis results in increased endothelial cell susceptibility to nitric oxide-induced apoptosis. Proc Natl Acad Sci USA 2002; 99: 6643-8.
75. Victor VM, Nuñez C, D'Ocon P, Taylor CT, Esplugues JV, Moncada S. Regulation of oxygen distribution in tissues by endothelial nitric oxide. Circ Res 2009; 104: 1178-83.
76. Hagen T, Taylor CT, Lam F, Moncada S. Redistribution of intracellular oxygen in hypoxia by nitric oxide: effect on HIF1 alpha. Science 2003; 302: 1975-8.
77. Devary Y, Rosette C, DiDonato JA, Karin M. NF-kappa B activation by ultraviolet light not dependent on a nuclear signal. Science 1993; 261: 1442-5.
78. Gloire G, Piette J. Redox regulation of nuclear post-translational modifications during NF-kappaB activation. Antioxid Redox Signal 2009; 11: 2209-22.
79. Adam-Vizi V, Chinopoulos C. Bioenergetics and the formation of mitochondrial reactive oxygen species. Trends Pharmacol Sci 2006; 27: 639-45.
80. Toogood PL. Mitochondrial drugs. Current Opinion in Chemical Biology 2008; 12: 457-63.
81. Fruehauf JP, Meyskens FL Jr. Reactive oxygen species: a breath of life or death? Clin Cancer Res 2007; 13: 789-94.
82. Kohanski MA, Dwyer DJ, Hayete B, Lawrence CA, Collins JJ. A common mechanism of cellular death induced by bactericidal antibiotics. Cell 2007; 130: 797-810.
83. Fantin VR, Leder P. Mitochondriotoxic compounds for cancer therapy. Oncogene 2006; 25: 4787-97.
84. Buzzai M, Jones RG, Amaravadi RK, et al. Systemic treatment with the antidiabetic drug metformin selectively impairs p53- deficient tumor cell growth. Cancer Res 2007; 67: 6745-52.
85. Neuzil J, Tomasetti M, Zhao Y, et al. Vitamin E analogs, a novel group of 'mitocans,' as anticancer agents: the importance of being redox-silent. Mol Pharmacol 2007; 71: 1185-99.
86. Wender PA, Jankowski OD, Longcore K, Tabet EA, Seto H, Tomikawa T. Correlation of F0F1-ATPase inhibition and antiproliferative activity of apoptolidin analogues. Org Lett 2006; 8: 589-92.
87. Johnson KM, Cleary J, Fierke CA, Opipari AW Jr, Glick GD. Mechanistic basis for therapeutic targeting of the mitochondrial F1F0-ATPase. ACS Chem Biol 2006; 1: 304-8.
88. Gledhill JR, Walker JE. Inhibition sites in F1-ATPase from bovine heart mitochondria. Biochem J 2005; 386: 591-8.
89. Gong Y, Sohn H, Xue L, Firestone GL, Bjeldanes LF. 3,30- Diindolylmethane is a novel mitochondrial H+-ATP synthase inhibitor that can induce p21Cip1/Waf1 expression by induction of oxidative stress in human breast cancer cells. Cancer Res 2006; 66: 4880-7.
90. Gledhill JR, Walker JE. Inhibitors of the catalytic domain of mitochondrial ATP synthase. Biochem Soc Trans 2006; 34: 989-92.
91. Cleary J, Johnson KM, Opipari AW Jr, Glick GD. Inhibition of the mitochondrial F1F0-ATPase by ligands of the peripheral benzodiazepine receptor. Bioorg Med Chem Lett 2007; 17: 1667-70.
92. Bhagavathula N, Nerusu KC, Hanosh A, et al. 7-Chloro-5-(4- hydroxyphenyl)-1-methyl-3-(naphthalene-2-ylmethyl)-3,4-dihydro-1Hbenzo[b][1,4]diazepin-2(3H)-one (Bz-423) a benzodiazepine, suppresses keratinocyte proliferation and has antipsoriatic activity in the human skin-severe, combined immunodeficient mouse transplant model. J Pharmacol Exp Therapeut 2008; 324: 938-47.
93. Sundberg TB, Ney GM, Subramanian C, Opipari AW Jr, Glick GD. The immunomodulatory benzodiazepine Bz-423 inhibits Bcell proliferation by targeting c-myc protein for rapid and specific degradation. Cancer Res 2006; 66: 1775-82.
94. Johnson KM, Cleary J, Fierke CA, Opipari AW Jr, Glick GD. Mechanistic basis for therapeutic targeting of the mitochondrial F1F0-ATPase. ACS Chem Biol 2006; 1: 304-8.
95. Baur JA, Pearson KJ, Price NL, et al. Resveratrol improves health and survival of mice on a high-calorie diet. Nature 2006; 444: 337-42.
96. Baur JA, Sinclair DA. Therapeutic potential of resveratrol: the in vivo evidence. Nat Rev Drug Disc 2006; 5: 493-506.
97. Atwal KS, Wang P, Rogers WL, et al. Small molecule mitochondrial F1F0 ATPase hydrolase inhibitors as cardioprotective agents. Identification of 4-(N-arylimidazole) - substituted benzopyran derivatives as selective hydrolase inhibitors. J Med Chem 2004; 47: 1081-4.
98. Chipuk JE, Bouchier-Hayes L, Green DR. Mitochondrial outer membrane permeabilization during apoptosis: the innocent bystander scenario. Cell Death Differ 2006; 13: 1396-402.
99. Letai AG. Diagnosing and exploiting cancer's addiction to blocks in apoptosis. Nat Rev Cancer 2008; 8: 121-32.
100. James ML, Selleri S, Kassiou M. Development of ligands for the peripheral benzodiazepine receptor. Curr Med Chem 2006; 13: 1991-2001.
101. Yagoda N, von Rechenburg M, Zaganjor E, et al. RAS-RAF-MEKdependent oxidative cell death involving voltage-dependent anion channels. Nature 2007; 447: 864-8.
102. Berkenblit A, Eder JP Jr, Ryan DP, et al. Phase I clinical trial of STA-4783 in combination with paclitaxel in patients with refractory solid tumors. Clin Cancer Res 2007; 13: 584-90.
103. Huang P, Feng L, Oldham EA, Keating MJ, Plunkett W. Superoxide dismutase as a target for the selective killing of cancer cells. Nature 2000; 407: 390-5.
104. Balaban RS, Nemoto S, Finkel T. Mitochondria, oxidants, and aging. Cell 2005; 120: 483-95.
105. Houstis N, Rosen ED, Lander ES. Reactive oxygen species have a causal role in multiple forms of insulin resistance. Nature 2006 440: 944-8.
106. Asin-Cayuela J, Manas AR, James AM, Smith RA, Murphy MP. Fine-tuning the hydrophobicity of a mitochondria-targeted antioxidant. FEBS Lett 2004; 571: 9-16.
107. Smith RA, Porteous CM, Coulter CM, Murphy MP. Selective targeting of an antioxidant to mitochondria. Eur J Biochem 1999; 263: 709-16.
108. Murphy MP, Smith RA. Targeting antioxidants to mitochondria by conjugation to lipophilic cations. Annu Rev Pharmacol Toxicol 2007; 47: 629-56.
109. Smith RA, Adlam VJ, Blaikie FH, et al. Mitochondria-targeted antioxidants in the treatment of disease. Ann N Y Acad Sci 2008; 1147: 105-11.
110. Rodriguez-Cuenca S, Cochemé HM, Logan E, et al. Consequences of long-term oral administration of the mitochondria-targeted antioxidant MitoQ to wild-type mice. Free Radic Biol Med 2010; 48: 161-72.
111. Ross MF, Kelso GF, Blaikie FH, et al. Lipophilic triphenylphosphonium cations as tools in mitochondrial bioenergetics and free radical biology. Biochemistry (Mosc.) 2005; 70: 222-30.
112. Jauslin ML, Meier T, Smith RA, Murphy MP. Mitochondriatargeted antioxidants protect Friedreich Ataxia fibroblasts from endogenous oxidative stress more effectively than untargeted antioxidants. FASEB J 2003; 17: 1972-4.
113. 2-mediated mitochondrial outgrowth. Am J Physiol Cell Physiol 2005; 288: C1440-50.
114. Smith RA, Porteous CM, Gane AM, Murphy MP. Delivery of bioactive molecules to mitochondria in vivo. Proc Natl Acad Sci USA 2003; 100: 5407-12.
115. Adlam VJ, Harrison JC, Porteous CM, et al. Targeting an antioxidant to mitochondria decreases cardiac ischemia-reperfusion injury. FASEB J 2005; 19: 1088-95.
116. Lipinski CA, Lombardo F, Dominy BW, Feeney PJ. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev 2001; 46: 3-26.
117. Wipf P, Xiao J, Jiang J, et al. Mitochondrial targeting of selective electron scavengers: synthesis and biological analysis of hemigramicidin- TEMPO conjugates. J Am Chem Soc 2005; 127: 12460-1.
118. Fink MP, Macias CA, Xiao J, et al. Hemigramicidin-TEMPO conjugates: novel mitochondria-targeted antioxidants. Crit Care Med 2007; 35: S461-7
119. Szeto HH. Mitochondria-targeted peptide antioxidants: novel neuroprotective agents. AAPS J 2006; 8: E521-31.
120. Spasojević I, Chen Y, Noel TJ, et al. Mn porphyrin-based superoxide dismutase (SOD) mimic, MnIIITE-2-PyP5+, targets mouse heart mitochondria. Free Radic Biol Med 2007; 42: 1193-200.
121. Lowes DA, Webster NR, Galley HF. Dehydroascorbic acid as preconditioner: protection from lipopolysaccharide induced mitochondrial damage. Free Radic Res 2010; 44: 283-92.
122. Packer L, Witt EH, Tritschler HJ. alpha-Lipoic acid as a biological antioxidant. Free Radic Biol Med 1995; 19: 227-50.
123. Ripcke J, Zarse K, Ristow M, Birringer M. Small-molecule targeting of the mitochondrial compartment with an endogenously cleaved reversible tag. Chembiochem. 2009; 10: 1689-96.
124. Roser KS, Brookes PS, Wojtovich AP, et al. Mitochondrial biotransformation of omega-(phenoxy)alkanoic acids, 3-(phenoxy) acrylic acids, and omega-(1-methyl-1H-imidazol-2-ylthio)alkanoic acids: a prodrug strategy for targeting cytoprotective antioxidants to mitochondria. Bioorg Med Chem. 2010; 18(4): 1441-8.
125. Nadanaciva S, Bernal A, Aggeler R, Capaldi R, Will Y. Target identification of drug induced mitochondrial toxicity using immunocapture based OXPHOS activity assays. Toxicol In Vitro 2007; 21: 902-11.
126. Lewis W, Day BJ, Copeland WC. Mitochondrial toxicity of NRTI antiviral drugs: an integrated cellular perspective. Nature 2003; 2: 812-22.
127. Dykens JA, Will Y. The significance of mitochondrial toxicity testing in drug development. Drug Disc Today 2007; 12: 777-85.
128. Rossignol R, Faustin B, Rocher C, Malgat M, Mazat JP, Letellier T. Mitochondrial threshold effects. Biochem J 2003; 370: 751-62.
129. Fox CJ, Hammerman PS, Thompson CB. Fuel feeds function: energy metabolism and the T-cell response. Nat Rev Immunol 2005; 5: 844-52.
130. Schumacher PT. Reactive oxygen species in cancer cells: live by the sword, die by the sword. Cancer Cell 2006; 10: 175-6.
131. Federico A, Morgillo F, Tuccillo C, Ciardiello F, Loguercio C. Chronic inflammation and oxidative stress in human carcinogenesis. Int J Cancer 2007; 121: 2381-6.
132. Ohshima H, Tatemichi M, Sawa T. Chemical basis of inflammation- induced carcinogenesis. Arch Biochem Biophys 2003; 417: 3-11.
133. Cebioglu M, Schild HH, Golubnitschaja O. Diabetes mellitus as a risk factor for cancer: stress or viral etiology? Infect Disord Drug Targets 2008; 8: 76-87.
134. Kern PA, Ranganathan S, Li C, Wood L, Ranganathan G. Adipose tissue tumour necrosis factor and interleukin- 6 expression in human obesity and insulin resistance. Am J Physiol 2001; 280: 745-51.
135. Szlosarek P, Charles KA, Balkwill FR. Tumour necrosis factoralpha as a tumour promoter. Eur J Cancer 2006; 42: 745-50.
136. Bonora E, Kiechl S, Willeit J, et al. Prevalence of IR in metabolic disorders: the Bruneck Study. Diabetes. 1988 47: 1643-9.
137. Haffner SM, Lehto S, Ronnemaa T, Pyorala K, Laakso M. Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. N Engl J Med 1998; 339: 229-34.
138. Saydah SH, Miret M, Sung J, Varas C, Gause D, Brancati FL. Postchallenge hyperglycemia and mortality in a national sample of U.S. adults. Diabetes Care 2001; 24: 1397-402.
139. Yip J, Facchini FS, Reaven GM. Resistance to insulin-mediated glucose disposal as a predictor of cardiovascular disease. J Clin Endocrinol Metab 1998; 83: 2773-6.
140. Du X, Edelstein D, Obici S, Higham N, Zou MH, Brownlee M. Insulin resistance reduces arterial prostacyclin synthase and eNOS activities by increasing endothelial fatty acid oxidation. J Clin Invest. 2006; 116: 1071-80.
141. Semenkovich CF. Insulin resistance and atherosclerosis. J Clin Invest 2006; 116: 1813-22.
142. Nathan DM, Cleary PA, Backlund JY, et al. Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Study Research Group. Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes. N Engl J Med 2005; 353: 2643-53.
143. Riddle MC, Ambrosius WT, Brillon DJ, et al. Action to Control Cardiovascular Risk in Diabetes Investigators. Epidemiologic relationships between A1C and all-cause mortality during a median 3.4-year follow-up of glycemic treatment in the ACCORD trial. Diabetes Care 2010; 33: 983-90.
144. Li S, Brown MS, Goldstein JL. Bifurcation of insulin signaling pathway in rat liver: mTORC1 required for stimulation of lipogenesis, but not inhibition of gluconeogenesis. Proc Natl Acad Sci USA 2010; 107: 3441-6.
145. Schulman IH, Zhou MS. Vascular insulin resistance: a potential link between cardiovascular and metabolic diseases. Curr Hypertens Rep 2009; 11: 48-55.
146. Thandavarayan RA, Watanabe K, Ma M, et al. Dominant negative p38alpha mitogen-activated protein kinase prevents cardiac apoptosis and remodeling after streptozotocin-induced diabetes mellitus. Am J Physiol Heart Circ Physiol. 2009; 297: H911-9.
147. Liang Q, Carlson EC, Donthi RV, Kralik PM, Shen X, Epstein PN. Overexpression of metallothionein reduces diabetic cardiomyopathy. Diabetes 2002; 51: 174-81.
148. Lee Y, Naseem RH, Park BH, et al. Alpha-lipoic acid prevents lipotoxic cardiomyopathy in acyl CoA-synthase transgenic mice. Biochem Biophys Res Commun. 2006; 344: 446-52.
149. Cacicedo JM, Benjachareowong S, Chou E, Ruderman NB, Ido Y. Palmitate-induced apoptosis in cultured bovine retinal pericytes: roles of NAD(P)H oxidase, oxidant stress, and ceramide. Diabetes. 2005; 54: 1838-45.
150. Inoguchi T, Li P, Umeda F, et al. High glucose level and free fatty acid stimulate reactive oxygen species production through protein kinase C-dependent activation of NAD(P)H oxidase in cultured vascular cells. Diabetes. 2000; 49: 1939-45.
151. Borradaile NM, Han X, Harp JD, Gale SE, Ory DS, Schaffer JE. Disruption of endoplasmic reticulum structure and integrity in lipotoxic cell death. J Lipid Res 2006; 47: 2726-37.
152. Kabat A, Ponicke K, Salameh A, Mohr FW, Dhein S. Effect of a beta 2-adrenoceptor stimulation on hyperglycemia-induced endothelial dysfunction. J Pharmacol Exp Ther 2004; 308: 564-73.
153. Hipkiss AR. Does chronic glycolysis accelerate aging? Could this explain how dietary restriction works? Ann N Y Acad Sci 2006; 1067: 361-8.
154. Nishikawa T, Edelstein D, Du XL, et al. Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage. Nature 2000; 404: 787-90.
155. Turrens JF, Boveris A. Generation of superoxide anion by the NADH dehydrogenase of bovine heart mitochondria. Biochem J 1980; 191: 421-7.
156. Verkaart S, Koopman WJ, van Emst-de Vries SE, et al. Superoxide production is inversely related to complex I activity in inherited complex I deficiency. Biochim Biophys Acta 2007; 1772: 373-81.
157. Hernandez-Mijares A, Rocha M, Apostolova N, et al. Mitochondrial complex I impairment in leukocytes from type 2 diabetic patients. Free Radic Biol Med 2011; 50: 125-1.
158. Rotig A, de Lonlay P, Chretien D, et al. Aconitase and mitochondrial iron-sulphur protein deficiency in Friedreich ataxia. Nat Genet 1997; 17: 215-7.
159. Martin-Hernandez E, Garcia-Silva MT, Vara J, et al. Renal pathology in children with mitochondrial diseases. Pediatr Nephrol 2005; 20: 1299-305.
160. Diomedi-Camassei F, Di Giandomenico S, Santorelli FM, et al. COQ2 nephropathy: a newly described inherited mitochondriopathy with primary renal involvement. J Am Soc Nephrol 2007; 18: 2773-80.
161. Hausse AO, Aggoun Y, Bonnet D, et al. Idebenone and reduced cardiac hypertrophy in Friedreich's ataxia. Heart 2002; 87: 346-9.
162. Green K, Brand MD, Murphy MP. Prevention of mitochondrial oxidative damage as a therapeutic strategy in diabetes. Diabetes 2004; 53: S110-8.
163. Chacko BK, Reily C, Srivastava A, et al. Prevention of diabetic nephropathy in Ins2(+/)×(AkitaJ) mice by the mitochondriatargeted therapy MitoQ. Biochem J 2010; 432: 9-19.
164. Krauss S, Zhang CY, Scorrano L, et al. Superoxide-mediated activation of uncoupling protein 2 causes pancreatic beta cell dysfunction. J Clin Invest 2003; 112: 1831-42.
165. Ceriello A, Morocutti A, Mercuri F, et al. Defective intracellular antioxidant enzyme production in type 1 diabetic patients with nephropathy. Diabetes 2000; 49: 2170-7.
166. DeRubertis FR, Craven PA, Melhem MF. Acceleration of diabetic renal injury in the superoxide dismutase knockout mouse: effects of tempol. Metabolism 2007; 56: 1256-64.
167. Hinerfeld D, Traini MD, Weinberger RP, et al. Endogenous mitochondrial oxidative stress: neurodegeneration, proteomic analysis, specific respiratory chain defects, and efficacious antioxidant therapy in superoxide dismutase 2 null mice. J Neurochem 2004; 88: 657-67.
168. Asaba K, Tojo A, Onozato ML, Goto A, Fujita T. Double-edged action of SOD mimetic in diabetic nephropathy. J Cardiovasc Pharmacol 2007; 49: 13-9.
169. Mollsten A, Marklund SL, Wessman M, et al. A functional polymorphism in the manganese superoxide dismutase gene and diabetic nephropathy. Diabetes 2007; 56: 265-9.
170. de Haan JB, Stefanovic N, Nikolic-Paterson D, et al. Kidney expression of glutathione peroxidase-1 is not protective against streptozotocin-induced diabetic nephropathy. Am J Physiol Renal Physiol 2005; 289: F544-51.
171. Brezniceanu ML, Liu F, Wei CC, et al. Catalase overexpression attenuates angiotensinogen expression and apoptosis in diabetic mice. Kidney Int 2007; 71: 912-23.
172. dos Santos KG, Canani LH, Gross JL, Tschiedel B, Souto KE, Roisenberg I. The catalase -262C/T promoter polymorphism and diabetes complications in Caucasians with type 2 diabetes. Dis Markers 2006; 22: 355-9.
173. Hussain SA. Silymarin as an adjunct to glibenclamide therapy improves long-term and postprandial glycemic control and body mass index in type 2 diabetes. J Med Food 2007; 10: 543-7.
174. Kaneto H, Kajimoto Y, Miyagawa J, et al. Beneficial effects of antioxidants in diabetes: possible protection of pancreatic beta-cells against glucose toxicity. Diabetes 1999; 48: 2398-406.
175. Lortz S, Tiedge M. Sequential inactivation of reactive oxygen species by combined overexpression of SOD isoforms and catalase in insulin-producing cells. Free Radic Biol Med 2003; 34: 683-8.
176. Tanaka Y, Gleason CE, Tran PO, Harmon JS, Robertson RP. Prevention of glucose toxicity in HIT-T15 cells and Zucker diabetic fatty rats by antioxidants. Proc Natl Acad Sci USA 1999; 96: 10857-62.
177. Yamamoto M, Yamato E, Toyoda S, et al. Transgenic expression of antioxidant protein thioredoxin in pancreatic beta cells prevents progression of type 2 diabetes mellitus. Antioxid Redox Signal 2008; 10: 43-9.
178. Snow BJ, Rolfe FL, Lockhart MM, et al. A double-blind, placebocontrolled study to assess the mitochondria-targeted antioxidant MitoQ as a disease-modifying therapy in Parkinson's disease. Mov Disord 2010; 25: 1670-4.
179. Gane EJ, Weilert F, Orr DW, et al. The mitochondria-targeted antioxidant mitoquinone decreases liver damage in a phase II study of hepatitis C patients. Liver Int. 2010; 30: 1019-26.
180. Hillgartner FB, Salati LM, Goodridge AG. Physiological and molecular mechanisms involved in nutritional regulation of fatty acid synthesis. Physiol Rev 1995; 75: 47-76.
181. Hudgins LC, Hellerstein MK, Seidman CE, Neese RA, Tremaroli JD, Hirsch J. Relationship between carbohydrate-induced hypertriglyceridemia and fatty acid synthesis in lean and obese subjects. J Lipid Res 2000; 41: 595-604.
182. Anderson EJ, Yamazaki H, Neufer PD. Induction of endogenous uncoupling protein 3 suppresses mitochondrial oxidant emission during fatty acid-supported respiration. J Biol Chem 2007; 282: 31257-66.
183. Claycombe KJ, Jones BH, Standridge MK, et al. Moustaid-Moussa, N. Insulin increases fatty acid synthase gene transcription in human adipocytes. Am J Physiol 1998; 274: R1253-9.
184. Postic C, Girard J. The role of the lipogenic pathway in the development of hepatic steatosis. Diabetes Metab 2008; 34: 643-8.
185. Caldwell S, Lazo M. Is exercise an effective treatment for NASH? Knowns and unknowns. Ann Hepatol 2009; 8: S60-6.
186. Lupu R, Menendez JA. Targeting fatty acid synthase in breast and endometrial cancer: an alternative to selective estrogen receptor modulators? Endocrinol 2006; 147: 4056-66.
187. Menendez JA, Vazquez-Martin A, Ortega FJ, Fernandez-Real JM. Fatty acid synthase: association with insulin resistance, type 2 diabetes, and cancer. Clin. Chem 2009; 55: 425-38.
188. Federico A, Morgillo F, Tuccillo C, Ciardiello F, Loguercio C. Chronic inflammation and oxidative stress in human carcinogenesis. Int J Cancer 2007; 121: 2381-6.
189. Ohshima H, Tatemichi M, Sawa T. Chemical basis of inflammation- induced carcinogenesis. Arch. Biochem. Biophys 2003; 417: 3-11.