Oxalomalate, a competitive inhibitor of NADP+ -dependent isocitrate dehydrogenase, regulates lipid peroxidation-mediated apoptosis in U937 cells.
Membrane lipid peroxidation processes yield products that may react with DNA and proteins to cause oxidative modifications. Recently, we demonstrated that the control of cytosolic redox balance and the cellular defense against oxidative damage is one of the primary functions of cytosolic NADP+ -dependent isocitrate dehydrogenase (IDPc) through to supply NADPH for antioxidant systems. The protective role of IDPc against lipid peroxidation-mediated apoptosis in U937 cells was investigated in control and cells pre-treated with oxlalomalate, a competitive inhibitor of IDPc. Upon exposure to 2,2'-azobis (2-amidinopropane) hydrochloride (AAPH) to U937 cells, which induces lipid peroxidation in membranes, the susceptibility to apoptosis was higher in oxalomalate-treated cells as compared to control cells. The results suggest that IDPc plays an important protective role in apoptosis of U937 cells induced by lipid peroxidation-mediated oxidative stress.
Yang
Eun Sun
ES
Department of Biochemistry, College of Natural Sciences, Kyungpook National University, Taegu 702-701, South Korea.
Yang
Joon-Hyuck
JH
Park
Ji Eun
JE
Park
Jeen-Woo
JW
D000578:Amidines / Q000737:chemistry; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis; D001667:Binding, Competitive; D002469:Cell Separation; D003600:Cytosol / Q000378:metabolism; D004247:DNA / Q000737:chemistry; D005434:Flow Cytometry; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D007521:Isocitrate Dehydrogenase / Q000737:chemistry*; D015227:Lipid Peroxidation; D008856:Microscopy, Fluorescence; D009249:NADP / Q000737:chemistry*; D010070:Oxalates / Q000737:chemistry / Q000494:pharmacology*; D016877:Oxidants / Q000494:pharmacology; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D017382:Reactive Oxygen Species; D013997:Time Factors; D020298:U937 Cells
D000578:Amidines; D000975:Antioxidants; D010070:Oxalates; D016877:Oxidants; D017382:Reactive Oxygen Species; C015407:oxalomalic acid; D009249:NADP; C046728:2,2'-azobis(2-amidinopropane); D004247:DNA; D007521:Isocitrate Dehydrogenase; C039355:isocitrate dehydrogenase (NADP+); D005978:Glutathione