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Inactivation of NADP+-dependent isocitrate dehydrogenase by lipid peroxidation products.
Free Radic Res. 2004 Mar; 38(3):241-9.FR

Abstract

Membrane lipid peroxidation processes yield products that may react with proteins to cause oxidative modification. Recently, we demonstrated that the control of cytosolic and mitochondrial redox balance and oxidative damage is one of the primary functions of NADP+-dependent isocitrate dehydrogenase (ICDH) through to supply NADPH for antioxidant systems. When exposed to lipid peroxidation products, such as malondialdehyde (MDA), 4-hydroxynonenal (HNE) and lipid hydroperoxide, ICDH was susceptible to oxidative damage, which was indicated by the loss of activity and the formation of carbonyl groups. The structural alterations of modified enzymes were indicated by the change in thermal stability, intrinsic tryptophan fluorescence and binding of the hydrophobic probe 8-anilino 1-napthalene sulfonic acid. Upon exposure to 2,2'-azobis(2-amidinopropane) hydrochloride (AAPH), which induces lipid peroxidation in membrane, a significant decrease in both cytosolic and mitochondrial ICDH activities were observed in U937 cells. Using immunoprecipitation and immunoblotting, we were able to isolate and positively identify HNE adduct in mitochondrial ICDH from AAPH-treated U937 cells. The lipid peroxidation-mediated damage to ICDH may result in the perturbation of the cellular antioxidant defense mechanisms and subsequently lead to a prooxidant condition.

Authors+Show Affiliations

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

Pub Type(s)

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

Language

eng

PubMed ID

15129732

Citation

Yang, Joon-Hyuck, et al. "Inactivation of NADP+-dependent Isocitrate Dehydrogenase By Lipid Peroxidation Products." Free Radical Research, vol. 38, no. 3, 2004, pp. 241-9.
Yang JH, Yang ES, Park JW. Inactivation of NADP+-dependent isocitrate dehydrogenase by lipid peroxidation products. Free Radic Res. 2004;38(3):241-9.
Yang, J. H., Yang, E. S., & Park, J. W. (2004). Inactivation of NADP+-dependent isocitrate dehydrogenase by lipid peroxidation products. Free Radical Research, 38(3), 241-9.
Yang JH, Yang ES, Park JW. Inactivation of NADP+-dependent Isocitrate Dehydrogenase By Lipid Peroxidation Products. Free Radic Res. 2004;38(3):241-9. PubMed PMID: 15129732.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Inactivation of NADP+-dependent isocitrate dehydrogenase by lipid peroxidation products. AU - Yang,Joon-Hyuck, AU - Yang,Eun Sun, AU - Park,Jeen-Woo, PY - 2004/5/8/pubmed PY - 2004/9/24/medline PY - 2004/5/8/entrez SP - 241 EP - 9 JF - Free radical research JO - Free Radic Res VL - 38 IS - 3 N2 - Membrane lipid peroxidation processes yield products that may react with proteins to cause oxidative modification. Recently, we demonstrated that the control of cytosolic and mitochondrial redox balance and oxidative damage is one of the primary functions of NADP+-dependent isocitrate dehydrogenase (ICDH) through to supply NADPH for antioxidant systems. When exposed to lipid peroxidation products, such as malondialdehyde (MDA), 4-hydroxynonenal (HNE) and lipid hydroperoxide, ICDH was susceptible to oxidative damage, which was indicated by the loss of activity and the formation of carbonyl groups. The structural alterations of modified enzymes were indicated by the change in thermal stability, intrinsic tryptophan fluorescence and binding of the hydrophobic probe 8-anilino 1-napthalene sulfonic acid. Upon exposure to 2,2'-azobis(2-amidinopropane) hydrochloride (AAPH), which induces lipid peroxidation in membrane, a significant decrease in both cytosolic and mitochondrial ICDH activities were observed in U937 cells. Using immunoprecipitation and immunoblotting, we were able to isolate and positively identify HNE adduct in mitochondrial ICDH from AAPH-treated U937 cells. The lipid peroxidation-mediated damage to ICDH may result in the perturbation of the cellular antioxidant defense mechanisms and subsequently lead to a prooxidant condition. SN - 1071-5762 UR - https://www.unboundmedicine.com/medline/citation/15129732/Inactivation_of_NADP+_dependent_isocitrate_dehydrogenase_by_lipid_peroxidation_products_ L2 - https://www.tandfonline.com/doi/full/10.1080/10715760310001657712 DB - PRIME DP - Unbound Medicine ER -