Modulation of NADP(+)-dependent isocitrate dehydrogenase in aging.
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 dehydrogenases (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-fed 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.
Kil
In Sup
IS
Department of Biochemistry, College of Natural Sciences, Kyungpook National University, Taegu, Korea.
Lee
Young Sup
YS
Bae
Young Seuk
YS
Huh
Tae Lin
TL
Park
Jeen-Woo
JW
D000367:Age Factors; D000375:Aging; D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D004396:Coloring Agents / Q000494:pharmacology; D003600:Cytosol / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000378:metabolism; D005452:Fluoresceins / Q000494:pharmacology; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007521:Isocitrate Dehydrogenase / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008291:Malate Dehydrogenase / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D009249:NADP / Q000737:chemistry* / Q000378:metabolism; D016877:Oxidants / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D017382:Reactive Oxygen Species; D013552:Swine; D013737:Testis / Q000378:metabolism; D013997:Time Factors
D004396:Coloring Agents; D005452:Fluoresceins; D016877:Oxidants; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D009249:NADP; C037631:2',7'-dichlorofluorescein; D006861:Hydrogen Peroxide; D008291:Malate Dehydrogenase; D007521:Isocitrate Dehydrogenase; D005978:Glutathione; D010100:Oxygen