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Modulation of NADP~+-dependent isocitrate dehydrogenase in aging

机译:衰老过程中NADP〜+依赖性异柠檬酸脱氢酶的调控

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摘要

NADPH is an important cofactor in many biosynthesis pathways and the regeneration of reduced glutathione, critically important in cellular defense against oxidative damage. It is mainly produced by glucose-6-phosphate dehydrogenase, malic enzyme, and NADP~+-specific isocitrate dehydro-genases (ICDHs). Here, we investigated age-related changes in ICDH activity and protein expression in IMR-90 human diploid fibroblast cells and tissues from Fischer 344 rats. We found that in IMR-90 cells the activity of cytosolic ICDH (IDPc) gradually increased with age up to the 46-48 population doubling level (PDL) and then gradually decreased at later PDL. 2',7'-Dichloro-fluorescein fluorescence which reflects intracellular ROS generation was increased with aging in IMR-90 cells. In ad libitum-fzd rats, we noted age-related, tissue-specific modulations of IDPc and mitochondrial ICDH (IDPm) activities and protein expression in the liver, kidney and testes. In contrast, ICDH activities and protein expression were not significantly modulated in diet-restricted rats. These data suggest that modulation of ICDH is an age-dependent and a tissue-specific phenomenon.
机译:NADPH在许多生物合成途径和还原型谷胱甘肽的再生中是重要的辅因子,这在细胞抵抗氧化损伤的防御中至关重要。它主要由6-磷酸葡萄糖脱氢酶,苹果酸酶和NADP〜+特异性异柠檬酸脱氢酶(ICDHs)产生。在这里,我们调查了Fischer 344大鼠IMR-90人二倍体成纤维细胞和组织中ICDH活性和蛋白质表达的年龄相关变化。我们发现在IMR-90细胞中,胞质ICDH(IDPc)的活性随着年龄的增长而逐渐增加,直至46-48人口倍增水平(PDL),然后在以后的PDL中逐渐降低。随着IMR-90细胞老化,反映细胞内ROS生成的2',7'-二氯荧光素荧光增加。在随意采食的大鼠中,我们注意到与年龄相关的组织特异性IDPc调节和线粒体ICDH(IDPm)活性以及肝脏,肾脏和睾丸中的蛋白质表达。相比之下,饮食限制的大鼠中ICDH活性和蛋白质表达没有显着调节。这些数据表明,ICDH的调节是一种年龄依赖性和组织特异性现象。

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