An SOD mimic protects NAD+-dependent isocitrate dehydrogenase against oxidative inactivation
An SOD mimic protects NAD+-dependent isocitrate dehydrogenase against oxidative inactivation
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DOI：
10.1080/10715760802209639
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发表时间：
2008-01-01
影响因子：
3.3
通讯作者：
Benov, Ludmil T.
中科院分区：
文献类型：
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作者：
Batinic-Haberle, Ines;Benov, Ludmil T.
异柠檬酸脱氢酶（ICD）催化异柠檬酸氧化脱羧为α-酮戊二酸，可以使用NAD（+）或NADP（+）作为辅因子。最近的研究表明，NADP（+）依赖性异柠檬酸脱氢酶作为细胞抗氧化剂的电子来源，对于防止氧化损伤非常重要。然而，ICD易受氧化失活的影响，这反过来又会损害细胞的抗氧化防御。本研究探讨了超氧化物歧化酶（SOD）模拟物MnTM-2-PyP 5+对SOD缺陷型大肠杆菌和糖尿病大鼠NADP（+）依赖性ICD失活的影响。结果表明，E.大肠杆菌ICD被超氧化物灭活，但灭活的酶被从头蛋白质合成所取代。糖尿病大鼠心脏ICD活性显著降低。MnTM-2-PyP 5+在两种模型中保护ICD。
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-PyP5+, 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-PyP5+ protected ICD in both models.