ROS acts as a double-edged sword in the pathogenesis of type 2 diabetes mellitus: Is Nrf2 a potential target for the treatment?

Mini-Reviews in Medicinal Chemistry

Volumn 11, Issue 12, 2011, Pages 1082-1092

  Wang, X ^a   Hai, C X ^a  

^a FOURTH MILITARY MEDICAL UNIVERSITY   (China)

Author keywords

Antioxidant; MAP kinase; Nrf2; PI3K Akt; Reactive oxygen species; Type 2 diabetes mellitus

Indexed keywords

BARDOXOLONE METHYL; COPPER ZINC SUPEROXIDE DISMUTASE; GLUCOSE TRANSPORTER 4; GLUTATHIONE PEROXIDASE 1; GLUTATHIONE REDUCTASE; GLUTATHIONE TRANSFERASE; GLYCOGEN SYNTHASE KINASE 3BETA; HEME OXYGENASE 1; INSULIN; KELCH LIKE ECH ASSOCIATED PROTEIN 1; MAMMALIAN TARGET OF RAPAMYCIN; MANGANESE SUPEROXIDE DISMUTASE; MITOGEN ACTIVATED PROTEIN KINASE; OLEANOLIC ACID; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA COACTIVATOR 1ALPHA; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN KINASE B; REACTIVE OXYGEN METABOLITE; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE (PHOSPHATE) DEHYDROGENASE (QUINONE); SOMATOMEDIN BINDING PROTEIN 1; SOMATOMEDIN BINDING PROTEIN 2; STRESS ACTIVATED PROTEIN KINASE; TRANSCRIPTION FACTOR NRF2; TRANSCRIPTION FACTOR PDX 1;

AEROBIC METABOLISM; ARTICLE; ATHEROSCLEROSIS; CARDIOVASCULAR RISK; CELL FATE; CELL PROTECTION; DISEASE ASSOCIATION; DISEASE COURSE; ENZYME ACTIVATION; ENZYME ACTIVITY; ENZYME INDUCTION; ENZYME PHOSPHORYLATION; GLOMERULUS FILTRATION RATE; GLUCOSE BLOOD LEVEL; GLUCOSE HOMEOSTASIS; GLUCOSE TRANSPORT; HUMAN; HYPERGLYCEMIA; IN VITRO STUDY; IN VIVO STUDY; INFLAMMATION; INSULIN BINDING; INSULIN RELEASE; INSULIN RESISTANCE; INSULIN SENSITIVITY; KIDNEY FUNCTION; LIPID STORAGE; LIPOLYSIS; MITOGENESIS; MUSCLE DEVELOPMENT; NITROSATIVE STRESS; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; OBESITY; OXIDATION REDUCTION POTENTIAL; OXIDATIVE STRESS; PANCREAS ISLET BETA CELL; PROTEIN ANALYSIS; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN LOCALIZATION; PROTEIN PROTEIN INTERACTION; RISK FACTOR; SIGNAL TRANSDUCTION; SURVIVAL; UPREGULATION;

DIABETES MELLITUS, TYPE 2; HUMANS; MOLECULAR TARGETED THERAPY; NF-E2-RELATED FACTOR 2; REACTIVE OXYGEN SPECIES;

EID: 82955180351     PISSN: 13895575     EISSN: 18755607     Source Type: Journal    
DOI: 10.2174/138955711797247761     Document Type: Article

References (96)

1. Muin, J.K.; Rodolfo, V.; Ann, A. Public Health Genomics Approachto Type 2 Diabetes. Diabetes, 2008, 57, 2911-4.
2. Leelayuwat, N.; Tunkumnerdthai, O.; Donsom, M.; Punyaek, N.;Manimanakorn, A.; Kukongviriyapan, U.; Kukongviriyapan, V. Analternative exercise and its beneficial effects on glycaemic controland oxidative stress in subjects with type 2 diabetes. Diabetes. Res. Clin. Pr., 2008, 82, 5-8.
3. Seghrouchni, I.; Drai, J.; Bannier, E.; Rivière, J.; Calmard, P.;Garcia, I.; Orgiazzi, J.; Revol, A. Oxidative stress parameters intype I, type II and insulin-treated type 2 diabetes mellitus; insulintreatment efficiency. Clin. Chim. Acta., 2002, 321, 89-96.
4. Laakso, M. Cardiovascular disease in type 2 diabetes: challenge fortreatment and prevention. J. Intern. Med., 2001, 249, 225-35.
5. Elgebaly, M.M.; Portik-Dobos, V.; Sachidanandam, K.; Rychly, D.; Malcom, D.; Johnson, M.H.; Ergul, A. Differential effects ofETA and ETB receptor antagonism on oxidative stress in type 2diabetes. Vasc. Pharmacol., 2007, 47, 125-30.
6. Nishikawa, T.; Kukidome, D.; Sonoda, K.; Fujisawa, K.; Matsuhisa, T.; Motoshima, H.; Matsumura, T.; Araki, E. Impact of mitochondrial ROS production in the pathogenesis of insulin resistance. Diabetes Res. Clin. Pr, 2007, 77, 161-4.
7. Gao, Z.; Yin, J.; Zhang, J.; Ward, R.; Martin, R.; Lefevre, M.;Cefalu, W.; Ye, J. Butyrate Improves Insulin Sensitivity and IncreasesEnergy Expenditure in Mice. Free Rad. Biol. Med., 2009, 43, 506-10.
8. Neri, S.; Signorelli, S.S.; Torrisi, B.; Pulvirenti, D.; Mauceri, B.;Abate, G.; Ignaccolo, L.; Bordonaro, F.; Cilio, D.; Calvagno, S.;Leotta, C. Effects of antioxidant supplementation on postprandialoxidative stress and endothelial dysfunction: A single-blind, 15-dayclinical trial in patients with untreated type 2 diabetes, subjectswith impaired glucose tolerance, and healthy controls. Clin. Ther., 2005, 27, 1764-73.
9. Robertson, R.P. Oxidative stress and impaired insulin secretion intype 2 diabetes. Curr. Opin. Pharmacol., 2006, 6, 615-9.
10. Ritchie, R. Evidence for a causal role of oxidative stress in themyocardial complications of insulin resistance. Heart Lung Circ., 2009, 18, 11-8.
11. Cai, L. Suppression of nitrative damage by metallothionein indiabetic heart contributes to the prevention of cardiomyopathy. Free Radic. Biol. Med., 2006, 41, 851-61.
12. Beckman, J.; Koppenol, W. Nitric oxide, superoxide, and peroxynitrite:the good, the bad, and ugly. Am. J. Physiol., 1996, 271, 1424-37.
13. Betteridge, D. What is oxidative stress? (Review). Metabolism, 2000, 49, 3-8.
14. Halliwell, B. Free radicals, antioxidants and human disease: Curiosity, cause or consequence. Lancet, 1994, 344, 721-4.
15. Droge, W. Free radicals in the physiological control of cell function. Physiol. Rev., 2002, 82, 47-95.
16. Ha, H.; Park, J.; Kim, Y.; Endou, H. Oxidative stress and chronic allograft nephropathy. (Review). Yonsei. Med. J., 2004, 45, 1049-52.
17. Morino, K.; Petersen, K.; Shulman, G. Molecular mechanisms ofinsulin resistance in humans and their potential links with mitochondrialdysfunction. Diabetes, 2006, 55, 9-15.
18. Tirosh, A.; Potashnik, R.; Bashan, N.; Rudich, A. Oxidative stressdisrupts insulin-induced cellular redistribution of insulin receptorsubstrate-1 and phosphatidylinositol 3-kinase in 3T3-L1 adipocytes:A putative cellular mechanism for impaired protein kinase Bactivation and GLUT4 translocation. J. Biol. Chem., 1999, 274, 10595-602.
19. K, M.; Kf, P.; GI, S. Molecular mechanisms of insulin resistancein humans and their potential links with mitochondrial dysfunction. Diabetes, 2006, 55(Suppl 2), 9-15.
20. Houstis, N.; Rosen, E.; Lander, E. Reactive oxygen species have acausal role in multiple forms of insulin resistance. Nature, 2006, 440, 944-8.
21. Robertson, R. Chronic oxidative stress as a central mechanism forglucose toxicity in pancreatic islet beta cells in diabetes. J. Biol. Chem., 2004, 279, 42351-4.
22. Lenzen, S.; Drinkgern, J.; Tiedge, M. Low antioxidant enzymegene expression in pancreatic islets compared with various othermouse tissues. Free Rad. Biol. Med., 1996, 20, 463-6.
23. Tiedge, M.; Lortz, S.; Drinkgern, J.; Lenzen, S. Relation betweenantioxidant enzyme gene expression and antioxidative defensestatus of insulin-producing cells. Diabetes, 1997, 46, 1733-42.
24. Kaneto, H.; Xu, G.; Song, K.H.; Suzuma, K.; Bonner-Weir, S.;Sharma, A.; Weir, G.C. Activation of the hexosamine pathwayleads to deterioration of pancreatic, β-cell function by provokingoxidative stress. J. Biol. Chem., 2001, 276, 31099-104.
25. Tanaka, Y.; Tran, P.; Harmon, J.; Robertson, R. A role for glutathioneperoxidase in protecting pancreatic beta cells against oxidativestress in a model of glucose toxicity. Proc. Natl. Acad. Sci. USA, 2002, 99, 12363-8.
26. May, J.M.; de Haen, C. The insulin-like effect of hydrogen peroxideon pathways of lipid synthesis in rat adipocytes. J. Biol. Chem., 1979, 254, 9017-21.
27. Evans, J.; Maddux, B.; Goldfine, I. The molecular basis for oxidativestress-induced insulin resistance. Antioxid. Redox Signal, 2005, 7, 1040-52.
28. Little, S.A.; de Haen, C. Effects of hydrogen peroxide on basal andhormone-stimulated lipolysis in perifused rat fat cells in relation tothe mechanism of action of insulin. J. Biol. Chem., 1980, 255, 10888-95.
29. Mahadev, K.; Wu, X.; Zilbering, A.; Zhu, L.; Todd, J.; Lawrence, R.; Goldstein, B.J. Hydrogen Peroxide Generated during CellularInsulin Stimulation Is Integral to Activation of the Distal InsulinSignaling Cascade in 3T3-L1 Adipocytes. J. Biol. Chem., 2001, 276, 48662-9.
30. Loh, K.; Deng, H.; Fukushima, A.; Cai, X.; Boivin, B.; Galic, S.;Bruce, C.; Shields, B.J.; Skiba, B.; Ooms, L.M.; Stepto, N.; Wu, B.; Mitchell, C.A.; Tonks, N.K.; Watt, M.J.; Febbraio, M.A.;Crack, P.J.; Andrikopoulos, S.; Tiganis, T. Reactive Oxygen SpeciesEnhance Insulin Sensitivity. Cell Metabolism, 2009, 10, 260-72.
31. Fridlyand, E.L.; Philipson, H.L. Does the Glucose-DependentInsulin Secretion Mechanism Itself Cause Oxidative Stress in Pancreatic[beta]-Cells? Diabetes, 2004, 53, 1942-8.
32. Pi, J.; Zhang, Q.; Fu, J.; Woods, C.G.; Hou, Y.; Corkey, B.E.;Collins, S.; Andersen, M.E. ROS signaling, oxidative stress andNrf2 in pancreatic beta-cell function. Toxicol. Appl. Pharmacol., 2009, 77-83.
33. Jaiswal, A.K. Nrf2 signaling in coordinated activation of antioxidantgene expression. Free Rad. Biol. Med., 2004, 36, 1199-207.
34. Chan, J.Y.; Kwong, M. Impaired expression of glutathione syntheticenzyme genes in mice with targeted deletion of the Nrf2 basic-leucine zipper protein. Biochim. Biophys. Acta, 2000, 1517, 19-26.
35. Chan, K.; Kan, Y. Nrf2 is essential for protection against acutepulmonary injury in mice. Proc. Natl. Acad. Sci. USA, 1999, 96, 12731-6.
36. Kensler, T.W.; Wakabayashi, N.; Biswal, S. Cell survival responsesto environmental stresses via the Keap1-Nrf2-ARE pathway. Ann. Rev. Pharmacol. Toxicol., 2007, 47, 89-116.
37. Dinkova-Kostova, A.; Holtzclaw, W.; Cole, R.; Itoh, K.; Wakabayashi, N.; Katoh, Y. Direct evidence that sulfhydryl groups ofKeap1 are the sensors regulating induction of phase 2 enzymes thatprotect against carcinogens and oxidants. Proc. Natl. Acad. Sci. USA., 2002, 99, 11908-13.
38. Ma, Q. Xenobiotic-activated receptors: from transcription to drugmetabolism to disease. Chem. Res. Toxicol., 2008, 21, 1651-71.
39. Wang, X.; Ye, X.L.; Liu, R.; Chen, H.L.; Bai, H.; Liang, X.;Zhang, X.D.; Wang, Z.; Li, W.L.; Hai, C.X. Antioxidant activitiesof oleanolic acid in vitro: possible role of Nrf2 and MAP kinases. Chem. Biol. Interact., 2010, 184, 328-37.
40. Wang, X.; Hai, C.X.; Liang, X.; Yu, S.X.; Zhang, W.; Li, Y.L. Theprotective effects of Acanthopanax senticosus Harms aqueous extractsagainst oxidative stress: role of Nrf2 and antioxidant enzymes.J. Ethnopharmacol., 2010, 127, 424-32.
41. St-Pierre, J.; Drori, S.; Uldry, M.; Silvaggi, J.; Rhee, J.; Jager, S.;Handschin, C.; Zheng, K.; Lin, J.; Yang, W.; Simon, D.; Bachoo, R.; Spiegelman, B. Suppression of reactive oxygen species andneurodegeneration by the PGC-1 transcriptional coactivators. Cell, 2006, 127, 397-408.
42. Nguyen, T.; Sherratt, P.; Pickett, C. Regulatory mechanisms controllinggene expression mediated by the antioxidant response element. Annu. Rev. Pharmacol. Toxicol., 2003, 43, 233-60.
43. Itoh, K.; Chiba, T.; Takahashi, S.; Ishii, T.; Igarashi, K.; Katoh, Y. An Nrf2/small Maf heterodimer mediates the induction of phase IIdetoxifying enzyme genes through antioxidant response elements. Biochem. Biophys. Res. Commun., 1997, 236, 313-22.
44. Favreau, L.; Pickett, C. The rat quinone reductase antioxidant responseelement. Identification of the nucleotide sequence required for basal and inducible activity and detection of antioxidant responseelement-binding proteins in hepatoma and non-hepatomacell lines. J. Biol. Chem., 1995, 270, 24468-74.
45. Wang, B.; Williamson, G. Detection of a nuclear protein whichbinds specifically to the antioxidant responsive element (ARE) ofthe human NAD(P) H:quinone oxidoreductase gene. Biochim. Biophys. Acta., 1994, 1219, 645-52.
46. Rushmore, T.; Pickett, C. Transcriptional regulation of the ratglutathione S-transferase Ya subunit gene. Characterization of a xenobiotic-responsive element controlling inducible expression byphenolic antioxidants. J. Biol. Chem., 1990, 265, 14648-53.
47. Galloway, D.; Blake, D.; McLellan, L. Regulation of gammaglutamylcysteinesynthetase regulatory subunit (GLCLR) gene expression:identification of the major transcriptional start site inHT29 cells. Biochim. Biophys. Acta., 1999, 1446, 47-56.
48. Hintze, K.; Keck, A.; Finley, J.; Jeffery, E. Induction of hepaticthioredoxin reductase activity by sulforaphane, both in Hepa1c1c7cells and in male Fisher 344 rats. J. Nutr. Biochem., 2003, 14, 173-9.
49. Ishii, T.; Itoh, K.; Sato, H.; Bannai, S. Oxidative stress-inducibleproteins in macrophages. Free Radic. Res., 1999, 31, 351-5.
50. He, X.; Kan, H.; Cai, L.; Ma, Q. Nrf2 is critical in defense againsthigh glucose-induced oxidative damage in cardiomyocytes. J. Mol. Cell Cardiol., 2009, 46, 47-58.
51. Jiang, T.; Huang, Z.; Lin, Y.; Zhang, Z.; Fang, D.; Zhang, D. Theprotective role of Nrf2 in STZ-induced diabetic nephropathy. Diabetes, 2010, 59, 850-60.
52. Aleksunes, L.; Reisman, S.; Yeager, R.; Goedken, M.; Klaassen, C. Nrf2 deletion impairs glucose tolerance and exacerbates hyperglycemiain Type 1 diabetic mice. J. Pharmacol. Exp. Ther., 2010, 333, 140-51.
53. Yoh, K.; Hirayama, A.; Ishizaki, K.; Yamada, A.; Takeuchi, M.;Yamagishi, S.; Morito, N.; Nakano, T.; Ojima, M.; Shimohata, H.;Itoh, K.; Takahashi, S.; Yamamoto, M. Hyperglycemia inducesoxidative and nitrosative stress and increases renal functional impairmentin Nrf2-deficient mice. Genes Cells, 2008, 13, 1159-70.
54. Cheng, X.; Siow, R.C.; Mann, G.E. Impaired redox signaling andantioxidant gene expression in endothelial cells in diabetes: a rolefor mitochondria and the Nrf2-Keap1 defense pathway. AntioxidRedox Signal, 2010, doi:10.1089/ars.2010.3283.
55. Yan, S.; Ramasamy, R.; Schmidt, A. Mechanisms of disease: advancedglycation end-products and their receptor in inflammationand diabetes complications. Nat. Clin. Pract. Endocrinol. Metab., 2008, 4, 285-93.
56. He, M.; Siow, R.; Sugden, D.; Gao, L.; Cheng, X.; Mann, G. Inductionof HO-1 and redox signaling in endothelial cells by advancedglycation end products: A role for Nrf2 in vascular protection indiabetes. Nutr. Metab. Cardiovasc. Dis., 2010, 21, 277-85.
57. Harrison, E.; McNally, S.; Devey, L.; Garden, O.; Ross, J.; Wigmore, S. Insulin induces heme oxygenase-1 through the phosphatidylinositol3-kinase/Akt pathway and the Nrf2 transcription factorin renal cells. FEBS J., 2006, 273, 2345-56.
58. Okouchi, M.; Okayama, N.; Alexander, J.; Aw, T. NRF2-dependent glutamate-L-cysteine ligase catalytic subunit expressionmediates insulin protection against hyperglycemia-induced brainendothelial cell apoptosis. Curr. Neurovasc. Res., 2006, 3, 249-61.
59. Langston, W.; Circu, M.; Aw, T. Insulin stimulation of gammaglutamylcysteineligase catalytic subunit expression increases endothelialGSH during oxidative stress: influence of low glucose. FreeRadic. Biol. Med., 2008, 45, 1591-9.
60. Lu, S.C. Regulation of glutathione synthesis. Mol. Aspects Med., 2009, 30, 42-59.
61. Urata, Y.; Yamamoto, H.; Goto, S.; Tsushima, H.; Akazawa, S.;Yamashita, S.; Nagataki, S.; Kondo, T. Long exposure to high glucoseconcentration impairs the responsive expression of cglutamylcysteinesynthetase by interleukin-1b and tumor necrosisfactor-a in mouse endothelial cells. J. Biol. Chem., 1996, 271, 15146-52.
62. Masahiro, O.; Naotsuka, O.; Alexander, S.; Aw, T. Nrf2-dependentglutamate-L-cysteine ligase catalytic subunit expression mediatesinsulin protection against hyperglycemia-induced brain endothelialcell apoptosis. Curr. Neurovasc. Res., 2006, 3, 249-61.
63. Beyer, T.; Xu, W.; Teupser, D.; Auf Dem Keller, U.; Bugnon, P.;Hildt, E.; Thiery, J.; Kan, Y.; Werner, S. Impaired liver regenerationin Nrf2 knockout mice: role of ROS-mediated insulin/IGF-1resistance. Embo. J., 2008, 27, 212-23.
64. Bloch-Damti, A.; Potashnik, R.; Gual, P.; Le Marchand-Brustel, Y.; Tanti, J.; Rudich, A.; Bashan, N. Differential effects of IRS1phosphorylated on Ser307 or Ser632 in the induction of insulin resistanceby oxidative stress. Diabetologia, 2006, 49, 2463-73.
65. Beyer, T.A.; Werner, S. The cytoprotective Nrf2 transcriptionfactor controls insulin receptor signaling in the regenerating liver. Cell Cycle, 2008, 7, 874-8.
66. Kamata, H.; Honda, S.; Maeda, S.; Chang, L.; Hirata, H.; Karin, M. Reactive oxygen species promote TNFalpha-induced death andsustained JNK activation by inhibiting MAP kinase phosphatases. Cell, 2006, 120, 649-61.
67. Beyer, T.A.; Xu, W.; Teupser, D.; Auf, D.K.U.; Bugnon, P.; Hildt, E.; Thiery, J.; Kan, Y.W.; Werner, S. Impaired liver regeneration inNrf2 knockout mice: role of ROS-mediated insulin/IGF-1 resistance. Embo. J., 2008, 27, 212-23.
68. Tanaka, Y.; Aleksunes, L.; Yeager, R.; Gyamfi, M.; Esterly, N.;Guo, G.; Klaassen, C. NF-E2-related factor 2 inhibits lipid accumulationand oxidative stress in mice fed a high-fat diet. J. Pharmacol. Exp. Ther., 2008, 325, 655-64.
69. Shin, S.; Wakabayashi, J.; Yates, M.; Wakabayashi, N.; Dolan, P.;Aja, S.; Liby, K.; Sporn, M.; Yamamoto, M.; Kensler, T. Role ofNrf2 in prevention of high-fat diet-induced obesity by synthetictriterpenoid CDDO-imidazolide. Eur. J. Pharmacol., 2009, 620, 138-44.
70. Wang, X.; Li, Y.L.; Wu, H.; Liu, J.Z.; Hu, J.X.; Liao, N.; Peng, J.;Cao, P.P.; Liang, X.; Hai, C.X. Antidiabetic Effect of OleanolicAcid: A Promising Use of a Traditional Pharmacological Agent. Phytother. Res., 2011, doi: 10.1002/ptr.3385.
71. Liby, K.; Hock, T.; Yore, M.M.; Suh, N.; Place, A.E.; Risingsong, R.; Williams, C.R.; Royce, D.B.; Honda, T.; Honda, Y.; Gribble, G.W.; Hill-Kapturczak, N.; Agarwal, A.; Sporn, M.B. The synthetictriterpenoids, CDDO and CDDO-imidazolide, are potent inducers of heme oxygenase-1 and Nrf2/ARE signaling. Cancer Res., 2005, 65, 4789-98.
72. Pergola, P.; Krauth, M.; Huff, J.; Ferguson, D.; Ruiz, S.; Meyer, C.;Warnock, D. Effect of Bardoxolone Methyl on Kidney Function inPatients with T2D and Stage 3b-4 CKD. Am. J. Nephrol., 2011, 33, 469-76.
73. Oh, K.S.; Kim, M.; Lee, J.; Kim, M.J.; Nam, Y.S.; Ham, J.E.; Shin, S.S.; Lee, C.M.; Yoon, M. Liver PPAR[alpha] and UCP2 are involvedin the regulation of obesity and lipid metabolism by swimtraining in genetically obese db/db mice. Biochem. Bioph. Res. Co., 2006, 345, 1232-9.
74. Ceriello, A. Controlling oxidative stress as a novel molecular approachto protecting the vascular wall in diabetes. Curr. Opin. Lipidol., 2006, 17, 510-8.
75. Stumvoll, M.; Haring, H. Glitazones: clinical effects and molecularmechanisms. Ann. Med., 2002, 34, 217-22.
76. Hernandez-Trujillo, Y.; Rodriguez-Esparragon, F.; Macias-Reyes, A.; Caballero-Hidalgo, A.; Rodriguez-Perez, J.C. Rosiglitazone butnot losartan prevents Nrf-2 dependent CD36 gene expression upregulationin an in vivo atherosclerosis model. Cardiovasc Diabetol., 2008, 7, 3-16.
77. Ferguson, H.E.; Thatcher, T.H.; Olsen, K.C.; Garcia-Bates, T.M.;Baglole, C.J.; Kottmann, R.M.; Strong, E.R.; Phipps, R.P.; Sime, P.J. Peroxisome proliferator-activated receptor-gamma ligands induceheme oxygenase-1 in lung fibroblasts by a PPARgammaindependent, glutathione-dependent mechanism. Am. J. Physiol. Lung Cell Mol. Physiol., 2009, 297, 912-9.
78. Park, E.Y.; Cho, I.J.; Kim, S.G. Transactivation of the PPARresponsiveenhancer module in chemopreventive glutathione Stransferasegene by the peroxisome proliferator-activated receptorgammaand retinoid X receptor heterodimer. Cancer Res., 2004, 64, 3701-13.
79. Ricote, M.; Li, A.; Wilson, T. Peroxisome Proliferator-activatedReceptor-α Is A Negative Regulator Of Macrophage Activation. Nature, 1998, 391, 79.
80. Puigserver, P.; Adelmant, G.; Wu, Z.; Fan, M.; Xu, J.; O'Malley, B.; Spiegelman, B. Activation of PPARgamma coactivator-1through transcription factor docking. Science, 1999, 286, 1368-71.
81. Puigserver, P.; Spiegelman, B. Peroxisome proliferatoractivatedreceptor-gamma coactivator 1 alpha (PGC-1 alpha): transcriptionalcoactivator and metabolic regulator. Endocr. Rev., 2003, 24, 78-90.
82. Handschin, C.; Spiegelman, B. Peroxisome proliferator-activatedreceptor gamma coactivator 1 coactivators, energy homeostasis, and metabolism. Endocr. Rev., 2006, 27, 728-35.
83. Anderson, R.; Barger, J.; Edwards, M.; Braun, K.; O'-Connor, C.;Prolla, T.; Weindruch, R. Dynamic regulation of PGC-1alpha localizationand turnover implicates mitochondrial adaptation in calorierestriction and the stress response. Aging Cell, 2008, 7, 101-11.
84. Spiegelman, B.M. Transcriptional control of energy homeostasisthrough the PGC1 coactivators. Novartis Found Symp., 2007, 286, 3-6.
85. Lin, J.; Wu, P.; Tarr, P.; Lindenberg, K.; St-Pierre, J.; Zhang, C.;Mootha, V.; Jager, S.; Vianna, C.; Reznick, R.; Cui, L.; Manieri, M.; Donovan, M.; Wu, Z.; Cooper, M.; Fan, M.; Rohas, L.;Zavacki, A.; Cinti, S.; Shulman, G.; Lowell, B.; Krainc, D.;Spiegelman, B. Defects in adaptive energy metabolism with CNS-linked hyperactivity in PGC-1alpha null mice. Cell, 2004, 119, 121-35.
86. Clark, J.; Simon, D.K. Transcribe to survive: transcriptional controlof antioxidant defense programs for neuroprotection in Parkinson'sdisease. Antioxid. Redox. Signal, 2009, 11, 509-28.
87. Hwang, Y.P.; Jeong, H.G. Ginsenoside Rb1 protects against 6-hydroxydopamine-induced oxidative stress by increasing hemeoxygenase-1 expression through an estrogen receptor-relatedPI3K/Akt/Nrf2-dependent pathway in human dopaminergic cells. Toxicol. Appl. Pharmacol., 2010, 242, 18-28.
88. Kang, K.W.; Lee, S.J.; Kim, S.G. Molecular mechanism of nrf2activation by oxidative stress. Antioxid. Redox. Signal, 2005, 7, 1664-73.
89. Kim, K.C.; Kang, K.A.; Zhang, R.; Piao, M.J.; Kim, G.Y.; Kang, M.Y.; Lee, S.J.; Lee, N.H.; Surh, Y.J.; Hyun, J.W. Up-regulation ofNrf2-mediated heme oxygenase-1 expression by eckol, a phlorotannincompound, through activation of Erk and PI3K/Akt. Int. J. Biochem. Cell Biol., 2010, 42, 297-305.
90. Stambolic, V.; Jr Woodgett. Mitogen inactivation of glycogensynthase kinase-3 beta in intact cells via serine 9 phosphorylation. Biochem. J., 1994, 303, 701-4.
91. Rojo, A.I.; Sagarra, M.R.; Cuadrado, A. GSK-3beta downregulatesthe transcription factor Nrf2 after oxidant damage: relevanceto exposure of neuronal cells to oxidative stress. J. Neurochem., 2008, 105, 192-202.
92. Jain, A.K.; Jaiswal, A.K. GSK-3beta acts upstream of Fyn kinase inregulation of nuclear export and degradation of NF-E2 related factor2. J. Biol. Chem., 2007, 282, 16502-10.
93. Bjelakovic, G.; Nikolova, D.; Gluud, L.L.; Simonetti, R.G.; Gluud, C. Mortality in randomized trials of antioxidant supplements forprimary and secondary prevention: systematic review and metaanalysis. JAMA, 2007, 297, 842-57.
94. Martin, D.; Salinas, M.; Lopez-Valdaliso, R.; Serrano, E.; Recuero, M.; Cuadrado, A. Effect of the Alzheimer amyloid fragmentAbeta(25-35) on Akt/PKB kinase and survival of PC12 cells. J. Neurochem., 2001, 78, 1000-8.
95. Martin, D.; Salinas, M.; Fujita, N.; Tsuruo, T.; Cuadrado, A. Ceramideand reactive oxygen species generated by H2O2 inducecaspase-3-independent degradation of Akt/protein kinase B. J. Biol. Chem., 2002, 277, 42943-52.
96. Woodgett, J.R. Recent advances in the protein kinase B signalingpathway. Curr. Opin. Cell Biol., 2005, 17, 150-7.