Cellular defense against heat shock-induced oxidative damage by mitochondrial NADP+ -dependent isocitrate dehydrogenase.
Heat shock may increase oxidative stress due to increased production of reactive oxygen species and/or the promotion of cellular oxidation events. Mitochondrial NADP+ -dependent isocitrate dehydrogenase (IDPm) produces NADPH, an essential reducing equivalent for the antioxidant system. The protective role of IDPm against heat shock in HEK293 cells, an embryonic kidney cell line, was investigated in control and cells transfected with the cDNA for IDPm, where IDPm activity was 6-7 fold higher than that in the control cells carrying the vector alone. Upon exposure to heat shock, the viability was lower and the protein oxidation, lipid peroxidation and oxidative DNA damage were higher in control cells as compared to HEK293 cells in which IDPm was over-expressed. We also observed the significant difference in the cellular redox status reflected by the endogenous production of reactive oxygen species, NADPH pool and GSH recycling between two cells. The results suggest that IDPm plays an important role as an antioxidant defense enzyme in cellular defense against heat shock through the removal of reactive oxygen species.
Kim
Hyun Jeong
HJ
Department of Biochemistry, College of Natural Sciences, Kyungpook National University, Taegu 702-701, South Korea.
Kang
Beom Sik
BS
Park
Jeen-Woo
JW
D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D002460:Cell Line; D002470:Cell Survival / Q000502:physiology; D004249:DNA Damage; D005978:Glutathione / Q000378:metabolism; D006358:Hot Temperature / Q000009:adverse effects*; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics / Q000378:metabolism*; D015227:Lipid Peroxidation / Q000502:physiology; D051379:Mice; D008928:Mitochondria / Q000378:metabolism*; D009249:NADP / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D014162:Transfection
D000975:Antioxidants; D017382:Reactive Oxygen Species; D009249:NADP; D007521:Isocitrate Dehydrogenase; D005978:Glutathione