Diabetes pp 272-287 | Cite as

Oxidative Stress in Diabetes

  • Krisztian Stadler
Part of the Advances in Experimental Medicine and Biology book series (AEMB)


Oxidative stress and diabetes, both Type 1 and Type 2 as well as their related conditions have been extensively studied. As diabetes, obesity and metabolic syndrome have reached at epidemic levels, there is a huge need and effort to understand the detailed molecular mechanisms of the possible redox imbalance, underlying the cause of pathology and progression of the disease. These studies provide new insights at cellular and subcellular levels to design effective clinical interventions. This chapter is intended to emphasize the latest knowledge and current evidence on the role of oxidative stress in diabetes as well as to discuss some key questions that are currently under discussion.


Oxidative Stress Insulin Resistance Aldose Reductase NLRP3 Inflammasome Spin Trap 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Wild S, Roglic G, Green A et al. Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care 2004; 27:1047–1053.PubMedCrossRefGoogle Scholar
  2. 2.
    Kowluru RA. Diabetic retinopathy: mitochondrial dysfunction and retinal capillary cell death. antioxid Redox Signal 2005; 7:1581–1587.PubMedCrossRefGoogle Scholar
  3. 3.
    Kowluru RA, Chan PS. Oxidative stress and diabetic retinopathy. Exp Diabetes Res 2007:436030.Google Scholar
  4. 4.
    Baynes JW. Role of oxidative stress in development of complications in diabetes. Diabetes 1991; 40:405–412.PubMedCrossRefGoogle Scholar
  5. 5.
    Baynes JW, Thorpe SR. Role of oxidative stress in diabetic complications: a new perspective on an old paradigm. Diabetes 1999; 48:1–9.PubMedCrossRefGoogle Scholar
  6. 6.
    Brownlee M. Biochemistry and molecular cell biology of diabetic complications. Nature 2001; 414:813–820.PubMedCrossRefGoogle Scholar
  7. 7.
    Ceriello A, Quatraro A, Giugliano D. Diabetes mellitus and hypertension: the possible role of hyperglycaemia through oxidative stress. Diabetologia 1993; 36:265–266.PubMedCrossRefGoogle Scholar
  8. 8.
    Thornalley PJ. Glycation in diabetic neuropathy: characteristics, consequences, causes and therapeutic options. Int Rev Neurobiol 2002; 50:37–57.PubMedCrossRefGoogle Scholar
  9. 9.
    Ceriello A, Quatraro A, Giugliano D. New insights on non-enzymatic glycosylation may lead to therapeutic approaches for the prevention of diabetic complications. Diabet Med 1992; 9:297–299.PubMedCrossRefGoogle Scholar
  10. 10.
    Ceriello A, Quagliaro L, Catone B et al. Role of hyperglycemia in nitrotyrosine postprandial generation. Diabetes Care 2002; 25:1439–1443.PubMedCrossRefGoogle Scholar
  11. 11.
    Wolff SP, Jiang ZY, Hunt JV. Protein glycation and oxidative stress in diabetes mellitus and ageing. free Radic Biol Med 1991; 10:339–352.PubMedCrossRefGoogle Scholar
  12. 12.
    The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. The Diabetes Control and Complications Trial Research Group. N Engl J Med 1993; 329:977–986.Google Scholar
  13. 13.
    Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. Lancet 1998; 352:837–853.Google Scholar
  14. 14.
    Gabbay KH, Merola LO, Field RA. Sorbitolpathway: presence innerve and cord with substrate accumulation in diabetes. Science 1966; 151:209–210.PubMedCrossRefGoogle Scholar
  15. 15.
    Engerman RL, Kern TS, Larson ME. Nerve conduction and aldose reductase inhibition during 5 years of diabetes or galactosaemia in dogs. Diabetologia 1994; 37:141–144.PubMedCrossRefGoogle Scholar
  16. 16.
    koya D, king GL. Protein kinase C activation and the development of diabetic complications. Diabetes 1998; 47:859–866.PubMedCrossRefGoogle Scholar
  17. 17.
    Xia P, Inoguchi T, kern TS et al. characterization of the mechanism for the chronic activation of diacylglycerol-proteinkinasecpathwayin diabetes and hypergalactosemia. Diabetes 1994;43:1122–1129.PubMedCrossRefGoogle Scholar
  18. 18.
    Giardino I, Edelstein D, Brownlee M. Nonenzymatic glycosylation in vitro and in bovine endothelial cells alters basic fibroblast growth factor activity. A model for intracellular glycosylation in diabetes. J Clin Invest 1994; 94:110–117.PubMedCrossRefGoogle Scholar
  19. 19.
    Shinohara M, thornalley PJ, Giardino I et al. overexpression of glyoxalase-I in bovine endothelial cells inhibits intracellular advanced glycation endproduct formation and prevents hyperglycemia-induced increases in macromolecular endocytosis. J clin Invest 1998; 101:1142–1147.PubMedCrossRefGoogle Scholar
  20. 20.
    Dyer DG, Dunn JA, thorpe SR et al. accumulation of Maillard reaction products in skin collagen in diabetes and aging. J Clin Invest 1993; 91:2463–2469.PubMedCrossRefGoogle Scholar
  21. 21.
    McClain DA. Hexosamines as mediators of nutrient sensing and regulation in diabetes. J Diabetes complications 2002; 16:72–80.PubMedCrossRefGoogle Scholar
  22. 22.
    Marshall S, Bacote V, traxinger rr. Discovery of a metabolic pathway mediating glucose-induced desensitization of the glucose transport system. Role of hexosamine biosynthesis in the induction of insulin resistance. J Biol chem 1991; 266:4706–4712.PubMedGoogle Scholar
  23. 23.
    Patti ME, Virkamaki A, landaker EJ et al. activation of the hexosamine pathway by glucosamine in vivo induces insulin resistance of early postreceptor insulin signaling events in skeletal muscle. Diabetes 1999; 48:1562–1571.PubMedCrossRefGoogle Scholar
  24. 24.
    Lee AY, chung SS. contributions of polyol pathway to oxidative stress in diabetic cataract. FASEB J 1999; 13:23–30.PubMedGoogle Scholar
  25. 25.
    Koya D, Jirousek MR, Lin YW et al. characterization of protein kinase C beta isoform activation on the gene expression of transforming growth factor-beta, extracellular matrix components and prostanoids in the glomeruli of diabetic rats. J Clin Invest 1997; 100:115–126.PubMedCrossRefGoogle Scholar
  26. 26.
    Studer RK, Craven PA, DeRubertis FR. Role for protein kinase C in the mediation of increased fibronectin accumulation by mesangial cells grown in high-glucose medium. Diabetes1993; 42:118–126.PubMedCrossRefGoogle Scholar
  27. 27.
    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; 49:1939–1945.PubMedCrossRefGoogle Scholar
  28. 28.
    Mclellan AC, Thornalley PJ, Benn J et al. Glyoxalase system in clinical diabetes mellitus and correlation with diabetic complications. Clin Sci (lond) 1994; 87:21–29.Google Scholar
  29. 29.
    abordo EA, Thornalley PJ. Synthesis and secretion of tumour necrosis factor-alpha by human monocytic THP-1 cells and chemotaxis induced by human serum albumin derivatives modified with methylglyoxal and glucose-derived advanced glycation endproducts. Immunol lett 1997; 58:139–147.PubMedCrossRefGoogle Scholar
  30. 30.
    Vlassara H, Brownlee M, Manogue KR et al. Cachectin/TNF and IL-1 inducedbyglucose-modifiedproteins: Role in normal tissue remodeling. Science 1988; 240:1546–1548.PubMedCrossRefGoogle Scholar
  31. 31.
    Wells L, Hart GW. O-GlcNAc turns twenty: functional implications for posttranslational modification of nuclear and cytosolic proteins with a sugar. FEBS lett2003; 546:154–158.PubMedCrossRefGoogle Scholar
  32. 32.
    Brownlee M. the pathobiology of diabetic complications: a unifying mechanism. Diabetes 2005; 54:1615–1625.PubMedCrossRefGoogle Scholar
  33. 33.
    Du XL, Edelstein D, Rossetti L et al. hyperglycemia-induced mitochondrial superoxide overproduction activates the hexosamine pathway and induces plasminogen activator inhibitor-1 expression by increasing Sp1 glycosylation. Proc Natl acad Sci U S A 2000; 97:12222–12226.PubMedCrossRefGoogle Scholar
  34. 34.
    Nishikawa T, Edelstein D, Du XL et al. Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage. Nature 2000; 404:787–790.PubMedCrossRefGoogle Scholar
  35. 35.
    Du X, Matsumura T, Edelstein D et al. Inhibition of GAPDH activitybypoly(ADP-ribose)polymerase activates three major pathways of hyperglycemic damage in endothelial cells. J Clin Invest 2003; 112:1049–1057.PubMedGoogle Scholar
  36. 36.
    Korshunov SS, Skulachev VP, Starkov AA. high protonic potential actuates a mechanism of production of reactive oxygen species in mitochondria. FEBS Lett 1997; 416:15–18.PubMedCrossRefGoogle Scholar
  37. 37.
    Ha HC, Snyder SH. Poly(ADP-ribose) polymerase is a mediator of necrotic cell death by ATP depletion. Proc Natl Acad Sci USA 1999; 96:13978–13982.PubMedCrossRefGoogle Scholar
  38. 38.
    Szabo C. Roles of poly(ADP-ribose) polymerase activation in the pathogenesis of diabetes mellitus and its complications. Pharmacol res 2005; 52:60–71.PubMedCrossRefGoogle Scholar
  39. 39.
    Obrosova IG. Increased sorbitol pathway activity generates oxidative stress in tissue sites for diabetic complications. Antioxid Redox Signal 2005; 7:!1543–1552.PubMedCrossRefGoogle Scholar
  40. 40.
    Obrosova IG. Diabetes and the peripheral nerve. Biochim Biophys Acta 2009; 1792:931–940.PubMedCrossRefGoogle Scholar
  41. 41.
    Obrosova IG, Drel VR, Oltman CL et al. Role of nitrosative stress in early neuropathy and vascular dysfunction in streptozotocin-diabetic rats. Am J Physiol Endocrinol Metab 2007; 293:E1645–E1655.PubMedCrossRefGoogle Scholar
  42. 42.
    Mabley JG, Soriano FG. Role of nitrosative stress and poly(ADP-ribose) polymerase activation in diabetic vascular dysfunction. Curr Vasc Pharmacol 2005; 3:247–252.PubMedCrossRefGoogle Scholar
  43. 43.
    Obrosova IG, Drel VR, Pacher P et al. oxidative-nitrosative stress andpoly(ADP-ribose) polymerase (PARP) activation in experimental diabetic neuropathy: the relation is revisited. Diabetes 2005; 54:3435–3441.PubMedCrossRefGoogle Scholar
  44. 44.
    Obrosova IG,LiF, Abatan OIet al. Role of poly(ADP-ribose) polymerase activation in diabetic neuropathy. Diabetes 2004; 53:711–720.PubMedCrossRefGoogle Scholar
  45. 45.
    Pacher P, Liaudet L, Soriano FG et al. the Role of poly(ADP-ribose) polymerase activation in the development of myocardial and endothelial dysfunction in diabetes. Diabetes 2002; 51:514!–521.PubMedCrossRefGoogle Scholar
  46. 46.
    Pacher P, Mabley JG, Soriano FG et al. activation of poly(ADP-ribose) polymerase contributes to the endothelial dysfunction associated with hypertension and aging. Int J Mol Med 2002; 9:659–664.PubMedGoogle Scholar
  47. 47.
    Pacher P, Szabo C. Role of poly(ADP-ribose) polymerase-1 activation in the pathogenesis of diabetic complications: endothelial dysfunction, as a common underlying theme. Antioxid Redox Signal 2005; 7:1568–1580.PubMedCrossRefGoogle Scholar
  48. 48.
    Szabo C, Zanchi A, Komjati K et al. Poly(ADP-ribose)polymeraseisactivatedinsubjectsatrisk of developing type 2 diabetes and is associated with impaired vascular reactivity. Circulation 2002; 106:2680–2686.PubMedCrossRefGoogle Scholar
  49. 49.
    Drel VR, Pacher P, Stevens MJ et al. aldose reductase inhibition counteracts nitrosative stress and poly(ADP-ribose) polymerase activation in diabetic rat kidney and high-glucose-exposed human mesangial cells. free radic Biol Med 2006; 40:1454–1465.PubMedCrossRefGoogle Scholar
  50. 50.
    Drel VR Pacher P, Vareniuk I et al. a peroxynitrite decomposition catalyst counteracts sensory neuropathy in streptozotocin-diabetic mice. Eur J Pharmacol 2007; 569:48–58.PubMedCrossRefGoogle Scholar
  51. 51.
    Ilnytska O, Lyzogubov VV, Stevens MJ et al. Poly(ADP-ribose) polymerase inhibition alleviates experimental diabetic sensory neuropathy. Diabetes 2006; 55:1686–1694.PubMedCrossRefGoogle Scholar
  52. 52.
    Obrosova IG, Mabley JG, Zsengeller Z et al. Role for nitrosative stress in diabetic neuropathy: evidence from studies with a peroxynitrite decomposition catalyst. FASEB J 2005; 19:401–403.PubMedGoogle Scholar
  53. 53.
    Obrosova IG, Pacher P, Szabo C et al. aldose reductase inhibition counteracts oxidative-nitrosative stress and poly(ADP-ribose) polymerase activation in tissue sites for diabetes complications. Diabetes 2005; 54:234–242.PubMedCrossRefGoogle Scholar
  54. 54.
    Pacher P, Vaslin A, Benko R et al. a new, potent poly(ADP-ribose) polymerase inhibitor improves cardiac and vascular dysfunction associated with advanced aging. J Pharmacol Exp ther 2004; 311:485–491.PubMedCrossRefGoogle Scholar
  55. 55.
    Suarez-Pinzon WL, Mabley JG, Strynadka K et al. an inhibitor of inducible nitric oxide synthase and scavenger of peroxynitrite prevents diabetes development in NoD mice. J Autoimmun 2001; 16:449–455.PubMedCrossRefGoogle Scholar
  56. 56.
    Beckman JS, Beckman TW, Chen J et al. apparenthydroxylradical production by peroxynitrite:implications for endothelial injury from nitric oxide and superoxide. Proc Natl acad Sci U S A 1990; 87:1620–1624.PubMedCrossRefGoogle Scholar
  57. 57.
    Szabo C, Ischiropoulos H, Radi R. Peroxynitrite: biochemistry, pathophysiology and development of therapeutics. Nat rev Drug Discov 2007; 6:662–680.PubMedCrossRefGoogle Scholar
  58. 58.
    Merenyi G, Lind J, Goldstein S et al. Peroxynitrous acid homolyzes into *oh and *No2 radicals. chem Res Toxicol 1998; 11:712–713.PubMedCrossRefGoogle Scholar
  59. 59.
    Pacher P, Beckman JS, Liaudet L. Nitric oxide and peroxynitrite in health and disease. Physiol rev 2007; 87:315–424.PubMedCrossRefGoogle Scholar
  60. 60.
    Du Y, Smith Ma, Miller CM et al. Diabetes-induced nitrative stress in the retina and correction by aminoguanidine. J Neurochem 2002; 80:771–779.PubMedCrossRefGoogle Scholar
  61. 61.
    Obrosova IG, Minchenko AG, Frank RN et al. Poly(ADP-ribose) polymerase inhibitors counteract diabetes-and hypoxia-induced retinal vascular endothelial growth factor overexpression. Int J Mol Med 2004; 14:55–64.PubMedGoogle Scholar
  62. 62.
    Sugawara R, Hikichi T, Kitaya N et al. Peroxynitrite decomposition catalyst, FP15, andpoly(ADP-ribose) polymerase inhibitor, PJ34, inhibit leukocyte entrapment in the retinal microcirculation of diabetic rats. curr Eye Res 2004; 29:11–16.PubMedCrossRefGoogle Scholar
  63. 63.
    Lenzen S, Drinkgern J, Tiedge M. low antioxidant enzyme gene expression in pancreatic islets compared with various other mouse tissues. Free Radic Biol Med 1996; 20:463–466.PubMedCrossRefGoogle Scholar
  64. 64.
    Tiedge M, Lortz S, Drinkgern J et al. Relation between antioxidant enzyme gene expression and antioxidative defense status of insulin-producing cells. Diabetes 1997; 46:1733–1742.PubMedCrossRefGoogle Scholar
  65. 65.
    Eizirik DL, Mandrup-Poulsen T. A choice of death—the signal-transduction of immune-mediated beta-cell apoptosis. Diabetologia 2001; 44:2115–2133.PubMedCrossRefGoogle Scholar
  66. 66.
    Evans JL, Goldfine ID, Maddux BA et al. Are oxidative stress-activated signaling pathways mediators of insulin resistance and beta-cell dysfunction? Diabetes 2003; 52:1–8.PubMedCrossRefGoogle Scholar
  67. 67.
    Robertson RP. Oxidative stress and impaired insulin secretion in type 2 diabetes. curr opin Pharmacol 2006; 6:615–619.PubMedCrossRefGoogle Scholar
  68. 68.
    Shimabukuro M, Ohneda M, Lee Y et al. Role of nitric oxide in obesity-induced beta cell disease. J Clin Invest 1997; 100:290–295.PubMedCrossRefGoogle Scholar
  69. 69.
    Schroder K, Zhou R, Tschopp J. The NLRP3 inflammasome: a sensor for metabolic danger? Science 2010; 327:296–300.PubMedCrossRefGoogle Scholar
  70. 70.
    Masters SL, Dunne A, Subramanian SL et al. Activation of the NLRP3 inflammasome by islet amyloid polypeptide provides a mechanism for enhancedIL-1beta in type2diabetes.NatImmunol2010; 11:897–904.Google Scholar
  71. 71.
    Haffner SM. Epidemiology of insulin resistance and its relation to coronary artery disease. Am J cardiol 1999; 84:11J–14J.PubMedCrossRefGoogle Scholar
  72. 72.
    Hanley AJ, Williams K, Stern MP et al. Homeostasis model assessment of insulin resistance in relation to the incidence of cardiovascular disease: the San Antonio Heart Study. Diabetes Care 2002; 25:1177–1184.PubMedCrossRefGoogle Scholar
  73. 73.
    Evans JL, Goldfine ID, Maddux BA et al. Oxidative stress and stress-activated signaling pathways: a unifying hypothesis of type 2 diabetes. Endocr rev 2002; 23:599–622.PubMedCrossRefGoogle Scholar
  74. 74.
    McGarry JD. Banting lecture 2001: dysregulation of fatty acid metabolism in the etiology of type 2 diabetes. Diabetes 2002; 51:7–18.PubMedCrossRefGoogle Scholar
  75. 75.
    Krebs M, Roden M. Nutrient-induced insulin resistance in human skeletal muscle. Curr Med Chem 2004; 11:901–908.PubMedCrossRefGoogle Scholar
  76. 76.
    Curtis R, Groarke A, Coughlan R et al. Psychological stress as a predictor of psychological adjustment and health status in patients with rheumatoid arthritis. Patient Educ Couns 2005; 59:192–198.PubMedCrossRefGoogle Scholar
  77. 77.
    Muoio DM, Newgard CB. obesity-related derangements in metabolic regulation. annu rev Biochem 2006; 75:367–401.PubMedCrossRefGoogle Scholar
  78. 78.
    Koves TR, Ussher JR, Noland RC et al. Mitochondrial overload and incomplete fatty acid oxidation contribute to skeletal muscle insulin resistance. cell Metab 2008; 7:45–56.PubMedCrossRefGoogle Scholar
  79. 79.
    Lowell BB, Shulman GI. Mitochondrial dysfunction and type 2 diabetes. Science 2005; 307:384–387.PubMedCrossRefGoogle Scholar
  80. 80.
    Anderson EJ, Lustig ME, Boyle KE et al. Mitochondrial H2O2 emission and cellular redox state link excess fat intake to insulin resistance in both rodents and humans. J clin Invest 2009.Google Scholar
  81. 81.
    Bonnard C, Durand A, Peyrol S et al. Mitochondrial dysfunction results from oxidative stress in the skeletal muscle of diet-induced insulin-resistant mice. J clin Invest 2008; 118:789–800.PubMedGoogle Scholar
  82. 82.
    Hancock CR, Chan DH, Chen M et al. high-fat diets cause insulin resistance despite an increase in muscle mitochondria. Proc Natl acad Sci U S A 2008; 105:7815–7820.PubMedCrossRefGoogle Scholar
  83. 83.
    Lee HY, Choi CS, Birkenfeld AL et al. targeted expression of catalase to mitochondria prevents age-associated reductions in mitochondrial function and insulin resistance. cell Metab 2010; 12:668–674.PubMedCrossRefGoogle Scholar
  84. 84.
    Hoehn kL, Salmon AB, Hohnen-Behrens C et al. Insulin resistance is a cellular antioxidant defense mechanism. Proc Natl acad Sci U S A 2009; 106:17787–17792.PubMedCrossRefGoogle Scholar
  85. 85.
    Saengsirisuwan V, Perez Fr, Sloniger JA et al. Interactions of exercise training and alpha-lipoicacid on insulin signaling in skeletal muscle of obese Zucker rats. AM J Physiol Endocrinol Metab 2004; 287:E529–E536.PubMedCrossRefGoogle Scholar
  86. 86.
    Marette A. Mediators of cytokine-induced insulin resistance in obesity and other inflammatory settings. Curr Opin Clin Nutr Metab care 2002; 5:377–383.PubMedCrossRefGoogle Scholar
  87. 87.
    Marette A. Molecular mechanisms of inflammation in obesity-linked insulin resistance. Int J Obes Relat Metab Disord 2003; 27 (Suppl 3):S46–S48.PubMedCrossRefGoogle Scholar
  88. 88.
    Sinha S, Perdomo G, Brown Nf et al. fatty acid-induced insulin resistance in L6 myotubes is prevented by inhibition of activation and nuclear localization of nuclear factor kappa B. J Biol chem 2004; 279:41294–41301.PubMedCrossRefGoogle Scholar
  89. 89.
    Yuan M, Konstantopoulos N, Lee J et al. Reversal of obesity-and diet-induced insulin resistance with salicylates or targeted disruption of Ikkbeta. Science 2001; 293:1673–1677.PubMedCrossRefGoogle Scholar
  90. 90.
    Ceriello A, Quagliaro L, D’amico M et al. Acute hyperglycemia induces nitrotyrosine formation and apoptosis in perfused heart from rat. Diabetes 2002; 51:1076–1082.PubMedCrossRefGoogle Scholar
  91. 91.
    Shimabukuro M, Zhou YT, Levi M et al. Fatty acid-induced beta cell apoptosis: a link between obesity and diabetes. Proc Natl acad Sci U S A 1998; 95:2498–2502.PubMedCrossRefGoogle Scholar
  92. 92.
    Elizalde M, Ryden M, van Harmelen V et al. Expression of nitric oxide synthases in subcutaneous adipose tissue of nonobese and obese humans. J lipid res 2000; 41:1244–1251.PubMedGoogle Scholar
  93. 93.
    Stadler K, Bonini MG, Dallas S et al. Involvement of inducible nitric oxide synthase in hydroxyl radical-mediated lipid peroxidation in streptozotocin-induced diabetes. Free Radic Biol Med 2008; 45:866–874.PubMedCrossRefGoogle Scholar
  94. 94.
    Hodara R, Norris Eh, Giasson BI et al. Functional consequences of alpha-synuclein tyrosine nitration: diminished binding to lipid vesicles and increased fibril formation. J Biol Chem 2004; 279:47746–47753.PubMedCrossRefGoogle Scholar
  95. 95.
    MacMillan-crow la, Crow JP, Kerby JD et al. Nitration and inactivation of manganese superoxide dismutase in chronic rejection of human renal allografts. Proc Natl acad Sci U S A 1996; 93:11853–11858.PubMedCrossRefGoogle Scholar
  96. 96.
    Quijano C, Hernandez-Saavedra D, Castro L et al. Reaction of peroxynitrite with Mn-superoxide dismutase. Role of the metal center in decomposition kinetics and nitration. J Biol chem 2001; 276:11631–11638.PubMedCrossRefGoogle Scholar
  97. 97.
    Esterbauer H, Schaur RJ, Zollner H. Chemistry and biochemistry of 4-hydroxynonenal, malonaldehyde and related aldehydes. Free Radic Biol Med 1991; 11:81–128.PubMedCrossRefGoogle Scholar
  98. 98.
    Perreault M, Marette A. Targeted disruption ofinducible nitric oxide synthase protects against obesity-linked insulin resistance in muscle. Nat Med 2001; 7:1138–1143.PubMedCrossRefGoogle Scholar
  99. 99.
    Fujimoto M, Shimizu N, Kunii K et al. A Role for iNOS in fasting hyperglycemia and impaired insulin signaling in the liver of obese diabetic mice. Diabetes 2005; 54:1340–1348.PubMedCrossRefGoogle Scholar
  100. 100.
    Charbonneau A, Marette A. INOS induction underlies lipid-induced hepatic insulin resistance in mice: Potential role of tyrosine nitration of insulin signaling proteins. Diabetes 2010.Google Scholar
  101. 101.
    Beckman JS. Oxidative damage and tyrosine nitration from peroxynitrite. Chemrestoxicol 1996; 9:836–844.Google Scholar
  102. 102.
    Ischiropoulos H. Biological tyrosine nitration: a pathophysiological function of nitric oxide and reactive oxygen species. Arch Biochem Biophys 1998; 356:1–11.PubMedCrossRefGoogle Scholar
  103. 103.
    Ischiropoulos H. Biological selectivity and functional aspects of protein tyrosine nitration. Biochem Biophys Res commun 2003; 305:776–783.PubMedCrossRefGoogle Scholar
  104. 104.
    Lai Ek, McCay PB, Noguchi T et al. In vivo spin-trapping of trichloromethyl radicals formed from ccl4. Biochem Pharmacol 1979; 28:2231–2235.PubMedCrossRefGoogle Scholar
  105. 105.
    Knecht KT, Mason RP. In vivo radical trapping and biliary secretion of radical adducts of carbon tetrachloride-derived free radical metabolites. Drug Metab Dispos 1988; 16:813–817.PubMedGoogle Scholar
  106. 106.
    Knecht KT, Mason RP. In vivo spin trapping of xenobiotic free radical metabolites. Arch Biochem Biophys 1993; 303:185–194.PubMedCrossRefGoogle Scholar
  107. 107.
    Sano T, Umeda F, Hashimoto T et al. Oxidative stress measurement by in vivo electron spin resonance spectroscopy in rats with streptozotocin-induced diabetes. Diabetologia 1998; 41:1355–1360.PubMedCrossRefGoogle Scholar
  108. 108.
    Stadler K, Jenei V, von Bolcshazy G et al. Increased nitric oxide levels as an early sign of premature aging in diabetes. Free Radic Biol Med 2003; 35:1240–1251.PubMedCrossRefGoogle Scholar
  109. 109.
    Stadler K, Bonini MG, Dallas S et al. Direct evidence of iNOS-mediated in vivo free radical production and protein oxidation in acetone-induced ketosis. am J Physiol Endocrinol Metab 2008; 295:E456–E462.PubMedCrossRefGoogle Scholar
  110. 110.
    Detweiler CD, Deterding LJ, Tomer KB et al. Immunological identification of the heart myoglobin radical formed by hydrogen peroxide. free radic Biol Med 2002; 33:364–369.PubMedCrossRefGoogle Scholar
  111. 111.
    Mason RP. Using anti-5,5-dimethyl-1-pyrroline N-oxide (anti-DMPo) to detect protein radicals in time and space with immuno-spin trapping. free radic Biol Med 2004; 36:1214–1223.PubMedCrossRefGoogle Scholar
  112. 112.
    Cassina P, Cassina A, Pehar M et al. Mitochondrial dysfunction in SOD1G93a-bearing astrocytes promotes motor neuron degeneration: prevention by mitochondrial-targeted antioxidants. J Neurosci 2008; 28:4115–4122.PubMedCrossRefGoogle Scholar
  113. 113.
    Bonini MG, Siraki AG, Atanassov BS et al. Immunolocalization of hypochlorite-induced, catalase-bound free radical formation in mouse hepatocytes. Free Radic Biol Med 2007; 42:530–540.PubMedCrossRefGoogle Scholar
  114. 114.
    Chatterjee S, Ehrenshaft M, Bhattacharjee S et al. Immuno-spin trapping of a posttranslational carboxypeptidase B1 radical formed by a dual role of xanthine oxidase and endothelial nitric oxide synthase in acute septic mice. Free Radic Biol Med 2009; 46:454–461.PubMedCrossRefGoogle Scholar
  115. 115.
    Ramirez DC, Mejiba SE, Mason RP. Copper-catalyzed protein oxidation and its modulation by carbon dioxide: enhancement of protein radicals in cells. J Biol Chem 2005; 280:27402–27411.PubMedCrossRefGoogle Scholar
  116. 116.
    Ruggiero C, Ehrenshaft M, Cleland E et al. High-fat diet induces an initial adaptation of mitochondrial bioenergetics in the kidney despite evident oxidative stress and mitochondrial ROS production. Am J Physiol Endocrinol Metab 2011; 300:E1047–E1058.PubMedCrossRefGoogle Scholar
  117. 117.
    Grimsrud PA, Picklo MJ Sr., Griffin TJ et al. Carbonylation of adipose proteins in obesity and insulin resistance: identification of adipocyte fatty acid-binding protein as a cellular target of 4-hydroxynonenal. Mol Cell Proteomics 2007; 6:624–637.PubMedCrossRefGoogle Scholar
  118. 118.
    Demozay D, Mas JC, Rocchi S et al. FALDH reverses the deleterious action of oxidative stress induced by lipid peroxidation product 4-hydroxynonenal on insulin signaling in 3t3-l1 adipocytes. Diabetes 2008; 57:1216–1226.PubMedCrossRefGoogle Scholar
  119. 119.
    Thuraisingham RC, Nott CA, Dodd SM et al. Increased nitrotyrosine staining in kidneys from patients with diabetic nephropathy. kidney Int 2000; 57:1968–1972.PubMedCrossRefGoogle Scholar
  120. 120.
    Cassina AM, Hodara R, Souza JM et al. Cytochrome c nitration by peroxynitrite. J Biol chem 2000; 275:21409–21415.PubMedCrossRefGoogle Scholar
  121. 121.
    Bonini MG, Rota C, Tomasi A et al. The oxidation of 2′,7′-dichlorofluorescin to reactive oxygen species: a self-fulfilling prophesy? Free Radic Biol Med 2006; 40:968–975.PubMedCrossRefGoogle Scholar
  122. 122.
    Wrona M, Patel k, Wardman P. Reactivity of 2′,7′-dichlorodihydrofluorescein and dihydrorhodamine 123 And their oxidized forms toward carbonate, nitrogen dioxide, and hydroxyl radicals. Free radic Biol Med 2005; 38:262–270.PubMedCrossRefGoogle Scholar
  123. 123.
    Rota C, Chignell CF, Mason RP. Evidence for free radical formation during the oxidation of 2′-7′-dichlorofluorescin to the fluorescent dye 2′-7′-dichlorofluorescein by horseradish peroxidase:possible implications for oxidative stress measurements. Free Radic Biol Med 1999; 27:873–881.PubMedCrossRefGoogle Scholar
  124. 124.
    Zielonka J, Kalyanaraman B. Hydroethidine-and MitoSOX-derived red fluorescence is not a reliable indicator of intracellular superoxide formation: another inconvenient truth. Free Radic Biol Med 2010; 48:983–1001.PubMedCrossRefGoogle Scholar

Copyright information

© Landes Bioscience and Springer Science+Business Media 2013

Authors and Affiliations

  • Krisztian Stadler
    • 1
  1. 1.Pennington Biomedical Research CenterBaton RougeUSA

Personalised recommendations