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Oxalomalate regulates ionizing radiation-induced apoptosis in mice.
Free Radic Biol Med. 2007 Jan 01; 42(1):44-51.FR

Abstract

Ionizing radiation induces the production of reactive oxygen species, which play an important causative role in apoptotic cell death. Recently, we demonstrated that the control of mitochondrial redox balance and the cellular defense against oxidative damage are primary functions of mitochondrial NADP(+)-dependent isocitrate dehydrogenase (IDPm) by supplying NADPH for antioxidant systems. In this paper, we demonstrate that modulation of IDPm activity in the kidneys of mice regulates ionizing radiation-induced apoptosis. When oxalomalate, a competitive inhibitor of IDPm, was administered to mice, inhibition of IDPm and enhanced susceptibility of apoptosis reflected by DNA fragmentation, the changes in mitochondria function, and the modulation of apoptotic marker proteins were observed upon exposure to 2 Gy of gamma-irradiation. We also observed a significant difference in the mitochondrial redox status between the kidneys of the control and the oxalomalate-administered mice. This study indicates that IDPm may play an important role in regulating the apoptosis induced by ionizing radiation, presumably, through acting as an antioxidant enzyme.

Authors+Show Affiliations

School of Life Sciences and Biotechnology, College of Natural Sciences, Kyungpook National University, Taegu 702-701, Korea.No affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

17157192

Citation

Lee, Jin Hyup, and Jeen-Woo Park. "Oxalomalate Regulates Ionizing Radiation-induced Apoptosis in Mice." Free Radical Biology & Medicine, vol. 42, no. 1, 2007, pp. 44-51.
Lee JH, Park JW. Oxalomalate regulates ionizing radiation-induced apoptosis in mice. Free Radic Biol Med. 2007;42(1):44-51.
Lee, J. H., & Park, J. W. (2007). Oxalomalate regulates ionizing radiation-induced apoptosis in mice. Free Radical Biology & Medicine, 42(1), 44-51.
Lee JH, Park JW. Oxalomalate Regulates Ionizing Radiation-induced Apoptosis in Mice. Free Radic Biol Med. 2007 Jan 1;42(1):44-51. PubMed PMID: 17157192.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Oxalomalate regulates ionizing radiation-induced apoptosis in mice. AU - Lee,Jin Hyup, AU - Park,Jeen-Woo, Y1 - 2006/09/23/ PY - 2006/06/12/received PY - 2006/08/25/revised PY - 2006/09/15/accepted PY - 2006/12/13/pubmed PY - 2007/2/16/medline PY - 2006/12/13/entrez SP - 44 EP - 51 JF - Free radical biology & medicine JO - Free Radic Biol Med VL - 42 IS - 1 N2 - Ionizing radiation induces the production of reactive oxygen species, which play an important causative role in apoptotic cell death. Recently, we demonstrated that the control of mitochondrial redox balance and the cellular defense against oxidative damage are primary functions of mitochondrial NADP(+)-dependent isocitrate dehydrogenase (IDPm) by supplying NADPH for antioxidant systems. In this paper, we demonstrate that modulation of IDPm activity in the kidneys of mice regulates ionizing radiation-induced apoptosis. When oxalomalate, a competitive inhibitor of IDPm, was administered to mice, inhibition of IDPm and enhanced susceptibility of apoptosis reflected by DNA fragmentation, the changes in mitochondria function, and the modulation of apoptotic marker proteins were observed upon exposure to 2 Gy of gamma-irradiation. We also observed a significant difference in the mitochondrial redox status between the kidneys of the control and the oxalomalate-administered mice. This study indicates that IDPm may play an important role in regulating the apoptosis induced by ionizing radiation, presumably, through acting as an antioxidant enzyme. SN - 0891-5849 UR - https://www.unboundmedicine.com/medline/citation/17157192/Oxalomalate_regulates_ionizing_radiation_induced_apoptosis_in_mice_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0891-5849(06)00592-2 DB - PRIME DP - Unbound Medicine ER -