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Oxalomalate, a competitive inhibitor of NADP+-dependent isocitrate dehydrogenase, enhances lipid peroxidation-mediated oxidative damage in U937 cells.
Arch Biochem Biophys. 2003 Aug 01; 416(1):31-7.AB

Abstract

Membrane lipid peroxidation processes yield products that may react with DNA and proteins to cause oxidative modifications. Cytosolic NADP+-dependent isocitrate dehydrogenase (ICDH) in U937 cells produces NADPH, an essential reducing equivalent for the antioxidant system. The protective role of ICDH against lipid peroxidation-mediated oxidative damage in U937 cells was investigated in control cells pre-treated with oxalomalate, a competitive inhibitor of ICDH. Upon exposure to 2,2'-azobis(2-amidinopropane) hydrochloride (AAPH) to U937 cells, which induces lipid peroxidation in membranes, the viability was lower and the protein oxidation, lipid peroxidation, and oxidative DNA damage, reflected by an increase in 8-hydroxy-2'-deoxyguanosine, were higher in oxalomalate-treated cells as compared to control cells. We also observed the significant increase in the endogenous production of reactive oxygen species, as measured by the oxidation of 2',7'-dichlorodihydrofluorescin, as well as the significant decrease in the intracellular GSH level in oxalomalate-treated U937 cells upon exposure to AAPH. These results suggest that ICDH plays an important role as an antioxidant enzyme in cellular defense against lipid peroxidation-mediated oxidative damage through the removal of reactive oxygen species.

Authors+Show Affiliations

Department of Biochemistry, College of Natural Sciences, Kyungpook National University, 702-701, Taegu, Republic of Korea.No affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

12859979

Citation

Yang, Joon-Hyuck, and Jeen-Woo Park. "Oxalomalate, a Competitive Inhibitor of NADP+-dependent Isocitrate Dehydrogenase, Enhances Lipid Peroxidation-mediated Oxidative Damage in U937 Cells." Archives of Biochemistry and Biophysics, vol. 416, no. 1, 2003, pp. 31-7.
Yang JH, Park JW. Oxalomalate, a competitive inhibitor of NADP+-dependent isocitrate dehydrogenase, enhances lipid peroxidation-mediated oxidative damage in U937 cells. Arch Biochem Biophys. 2003;416(1):31-7.
Yang, J. H., & Park, J. W. (2003). Oxalomalate, a competitive inhibitor of NADP+-dependent isocitrate dehydrogenase, enhances lipid peroxidation-mediated oxidative damage in U937 cells. Archives of Biochemistry and Biophysics, 416(1), 31-7.
Yang JH, Park JW. Oxalomalate, a Competitive Inhibitor of NADP+-dependent Isocitrate Dehydrogenase, Enhances Lipid Peroxidation-mediated Oxidative Damage in U937 Cells. Arch Biochem Biophys. 2003 Aug 1;416(1):31-7. PubMed PMID: 12859979.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Oxalomalate, a competitive inhibitor of NADP+-dependent isocitrate dehydrogenase, enhances lipid peroxidation-mediated oxidative damage in U937 cells. AU - Yang,Joon-Hyuck, AU - Park,Jeen-Woo, PY - 2003/7/16/pubmed PY - 2003/8/20/medline PY - 2003/7/16/entrez SP - 31 EP - 7 JF - Archives of biochemistry and biophysics JO - Arch Biochem Biophys VL - 416 IS - 1 N2 - Membrane lipid peroxidation processes yield products that may react with DNA and proteins to cause oxidative modifications. Cytosolic NADP+-dependent isocitrate dehydrogenase (ICDH) in U937 cells produces NADPH, an essential reducing equivalent for the antioxidant system. The protective role of ICDH against lipid peroxidation-mediated oxidative damage in U937 cells was investigated in control cells pre-treated with oxalomalate, a competitive inhibitor of ICDH. Upon exposure to 2,2'-azobis(2-amidinopropane) hydrochloride (AAPH) to U937 cells, which induces lipid peroxidation in membranes, the viability was lower and the protein oxidation, lipid peroxidation, and oxidative DNA damage, reflected by an increase in 8-hydroxy-2'-deoxyguanosine, were higher in oxalomalate-treated cells as compared to control cells. We also observed the significant increase in the endogenous production of reactive oxygen species, as measured by the oxidation of 2',7'-dichlorodihydrofluorescin, as well as the significant decrease in the intracellular GSH level in oxalomalate-treated U937 cells upon exposure to AAPH. These results suggest that ICDH plays an important role as an antioxidant enzyme in cellular defense against lipid peroxidation-mediated oxidative damage through the removal of reactive oxygen species. SN - 0003-9861 UR - https://www.unboundmedicine.com/medline/citation/12859979/Oxalomalate_a_competitive_inhibitor_of_NADP+_dependent_isocitrate_dehydrogenase_enhances_lipid_peroxidation_mediated_oxidative_damage_in_U937_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0003986103002911 DB - PRIME DP - Unbound Medicine ER -