Regulation of high glucose-induced apoptosis by mitochondrial NADP+-dependent isocitrate dehydrogenase.
A high concentration of glucose has been implicated as a causal factor in initiation and progression of diabetic kidney complications, and there is evidence to suggest that hyperglycemia increases the production of free radicals and oxidant stress. Recently, we demonstrated that the control of mitochondrial redox balance and the cellular defense against oxidative damage is one of the primary functions of mitochondrial NADP(+)-dependent isocitrate dehydrogenase (IDPm) to supply NADPH for antioxidant systems. In this report, we demonstrate that modulation of IDPm activity in HEK293 cells, an embryonic kidney cell line, regulates high glucose-induced apoptosis. When we examined the protective role of IDPm against high glucose-induced apoptosis with HEK293 cells transfected with the cDNA for mouse IDPm in sense and antisense orientations, a clear inverse relationship was observed between the amount of IDPm expressed in target cells and their susceptibility to apoptosis. The results suggest that IDPm plays an important protective role in apoptosis of HEK293 cells induced by a high concentration of glucose and may contribute to various pathologies associated with the long-term complications of diabetes.
Shin
Ai Hyang
AH
Department of Biochemistry, College of Natural Sciences, Kyungpook National University, Taegu 702-701, Republic of Korea.
Kil
In Sup
IS
Yang
Eun Sun
ES
Huh
Tae Lin
TL
Yang
Chae Ha
CH
Park
Jeen-Woo
JW
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D016373:DNA, Antisense / Q000235:genetics / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D006943:Hyperglycemia / Q000378:metabolism; D007521:Isocitrate Dehydrogenase / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology*; D016877:Oxidants / Q000096:biosynthesis; D010084:Oxidation-Reduction
D016373:DNA, Antisense; D016877:Oxidants; D006861:Hydrogen Peroxide; D007521:Isocitrate Dehydrogenase; C039355:isocitrate dehydrogenase (NADP+); D005947:Glucose