Oxalomalate, a competitive inhibitor of NADP+-dependent isocitrate dehydrogenase, regulates heat shock-induced apoptosis.
Heat shock may increase oxidative stress due to increased production of reactive oxygen species and/or the promotion of cellular oxidation events. Recently, we demonstrated that the control of cytosolic and mitochondrial redox balance and the cellular defense against oxidative damage is one of the primary functions of NADP(+)-dependent isocitrate dehydrogenase (ICDH) by supplying NADPH for antioxidant systems. The protective role of ICDH against heat shock-induced apoptosis in U937 cells was investigated in the control and the cells pre-treated with oxalomalate, a competitive inhibitor of ICDH. Upon exposure to heat shock, there was a distinct difference between the control cells and the cells pre-treated with 3mM oxalomalate for 3h in regard to apoptotic parameters, cellular redox status, and mitochondrial function. The oxalomalate pre-treated cells showed significant enhancement of apoptotic features such as activation of caspase-3, up-regulation of Bax, and down-regulation of Bcl-2 compared to the control cells upon exposure to heat shock. This study indicates that ICDH may play an important role in regulating the apoptosis induced by heat shock presumably through maintaining the cellular redox status.
Kim
Hyun Jeong
HJ
School of Life Sciences and Biotechnology, College of Natural Sciences, Kyungpook National University, Taegu, Republic of Korea.
Park
Jeen-Woo
JW
D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D015536:Down-Regulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018869:Heat-Shock Response / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000037:antagonists & inhibitors*; D009249:NADP / Q000378:metabolism*; D010070:Oxalates / Q000494:pharmacology*; D010084:Oxidation-Reduction; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D020298:U937 Cells; D015854:Up-Regulation
D004791:Enzyme Inhibitors; D010070:Oxalates; D019253:Proto-Oncogene Proteins c-bcl-2; C015407:oxalomalic acid; D009249:NADP; D007521:Isocitrate Dehydrogenase; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases