title: Oxalomalate, a competitive inhibitor of NADP+ -dependent isocitrate dehydrogenase, regulates lipid peroxidation-mediated apoptosis in U937 cells.
abstract: 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.
authors.affiliation: Department of Biochemistry, College of Natural Sciences, Kyungpook National University, Taegu 702-701, South Korea.
authors.forename: Eun Sun
authors.initials: ES
authors.lastname: Yang
authors.forename: Joon-Hyuck
authors.initials: JH
authors.lastname: Yang
authors.forename: Ji Eun
authors.initials: JE
authors.lastname: Park
authors.forename: Jeen-Woo
authors.initials: JW
authors.lastname: Park
mesh_terms: 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
chemical_list: 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