An SOD mimic protects NADP+-dependent isocitrate dehydrogenase against oxidative inactivation.
The isocitrate dehydrogenases (ICDs) catalyse the oxidative decarboxylation of isocitrate to alpha-ketoglutarate and can use either NAD(+) or NADP(+) as a cofactor. Recent studies demonstrate that the NADP(+)-dependent isocitrate dehydrogenase, as a source of electrons for cellular antioxidants, is important for protection against oxidative damage. ICD, however, is susceptible to oxidative inactivation, which in turn compromises cellular antioxidant defense. This study investigates the effect of a superoxide dismutase (SOD) mimic, MnTM-2-PyP(5+), on the inactivation of NADP(+)-dependent ICD in SOD-deficient Escherichia coli and in diabetic rats. The findings show that E. coli ICD is inactivated by superoxide, but the inactivated enzyme is replaced by de novo protein synthesis. Statistically significant decrease of ICD activity was found in the hearts of diabetic rats. MnTM-2-PyP(5+) protected ICD in both models.
Batinic-Haberle
Ines
I
Department of Radiation Oncology, Duke University Medical Center, Durham, NC 27710, USA.
Benov
Ludmil T
LT
D000154:Aconitate Hydratase / Q000378:metabolism; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000201:enzymology; D004789:Enzyme Activation; D004926:Escherichia coli / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism*; D016166:Free Radical Scavengers / Q000494:pharmacology*; D007521:Isocitrate Dehydrogenase / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008665:Metalloporphyrins / Q000494:pharmacology*; D009206:Myocardium / Q000201:enzymology*; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects; D014176:Protein Biosynthesis; D051381:Rats; D017208:Rats, Wistar; D026361:Reactive Nitrogen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism; D013997:Time Factors
D029968:Escherichia coli Proteins; D016166:Free Radical Scavengers; D008665:Metalloporphyrins; C502230:Mn(III) 5,10,15,20-tetrakis(N-methylpyridinium-2-yl)porphyrin; D026361:Reactive Nitrogen Species; D013481:Superoxides; D007521:Isocitrate Dehydrogenase; C039355:isocitrate dehydrogenase (NADP+); D013482:Superoxide Dismutase; D000154:Aconitate Hydratase