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Regulation of ionizing radiation-induced apoptosis by mitochondrial NADP+-dependent isocitrate dehydrogenase.
J Biol Chem. 2007 May 04; 282(18):13385-94.JB

Abstract

Ionizing radiation induces the production of reactive oxygen species, which play an important causative role in apoptotic cell death. By supplying NADPH for antioxidant systems, we recently demonstrated that the control of mitochondrial redox balance and the cellular defense against oxidative damage are some of the primary functions of mitochondrial NADP(+)-dependent isocitrate dehydrogenase (IDPm). In this study, we demonstrate that modulation of IDPm activity in U937 cells regulates ionizing radiation-induced apoptosis. When we examined the regulatory role of IDPm against ionizing radiation-induced apoptosis in U937 cells transfected with the cDNA for mouse IDPm in sense and antisense orientations, a clear inverse relationship was observed between the amount of IDPm expressed in target cells and their susceptibility to apoptosis. Upon exposure to 2 gray gamma-irradiation, there was a distinct difference between the IDPm transfectant cells in regard to the morphological evidence of apoptosis, DNA fragmentation, cellular redox status, oxidative damage to cells, mitochondrial function, and the modulation of apoptotic marker proteins. In addition, transfection of HeLa cells with an IDPm small interfering RNA decreased the activity of IDPm, enhancing the susceptibility of radiation-induced apoptosis. Taken together, these results indicate that IDPm may play an important role in regulating the apoptosis induced by ionizing radiation, and the effect of IDPm small interfering RNA on HeLa cells offers the possibility of developing a modifier of radiation therapy.

Authors+Show Affiliations

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

Pub Type(s)

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

Language

eng

PubMed ID

17350954

Citation

Lee, Jin Hyup, et al. "Regulation of Ionizing Radiation-induced Apoptosis By Mitochondrial NADP+-dependent Isocitrate Dehydrogenase." The Journal of Biological Chemistry, vol. 282, no. 18, 2007, pp. 13385-94.
Lee JH, Kim SY, Kil IS, et al. Regulation of ionizing radiation-induced apoptosis by mitochondrial NADP+-dependent isocitrate dehydrogenase. J Biol Chem. 2007;282(18):13385-94.
Lee, J. H., Kim, S. Y., Kil, I. S., & Park, J. W. (2007). Regulation of ionizing radiation-induced apoptosis by mitochondrial NADP+-dependent isocitrate dehydrogenase. The Journal of Biological Chemistry, 282(18), 13385-94.
Lee JH, et al. Regulation of Ionizing Radiation-induced Apoptosis By Mitochondrial NADP+-dependent Isocitrate Dehydrogenase. J Biol Chem. 2007 May 4;282(18):13385-94. PubMed PMID: 17350954.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Regulation of ionizing radiation-induced apoptosis by mitochondrial NADP+-dependent isocitrate dehydrogenase. AU - Lee,Jin Hyup, AU - Kim,Sung Youl, AU - Kil,In Sup, AU - Park,Jeen-Woo, Y1 - 2007/03/09/ PY - 2007/3/14/pubmed PY - 2007/6/15/medline PY - 2007/3/14/entrez SP - 13385 EP - 94 JF - The Journal of biological chemistry JO - J Biol Chem VL - 282 IS - 18 N2 - Ionizing radiation induces the production of reactive oxygen species, which play an important causative role in apoptotic cell death. By supplying NADPH for antioxidant systems, we recently demonstrated that the control of mitochondrial redox balance and the cellular defense against oxidative damage are some of the primary functions of mitochondrial NADP(+)-dependent isocitrate dehydrogenase (IDPm). In this study, we demonstrate that modulation of IDPm activity in U937 cells regulates ionizing radiation-induced apoptosis. When we examined the regulatory role of IDPm against ionizing radiation-induced apoptosis in U937 cells transfected with the cDNA for mouse IDPm in sense and antisense orientations, a clear inverse relationship was observed between the amount of IDPm expressed in target cells and their susceptibility to apoptosis. Upon exposure to 2 gray gamma-irradiation, there was a distinct difference between the IDPm transfectant cells in regard to the morphological evidence of apoptosis, DNA fragmentation, cellular redox status, oxidative damage to cells, mitochondrial function, and the modulation of apoptotic marker proteins. In addition, transfection of HeLa cells with an IDPm small interfering RNA decreased the activity of IDPm, enhancing the susceptibility of radiation-induced apoptosis. Taken together, these results indicate that IDPm may play an important role in regulating the apoptosis induced by ionizing radiation, and the effect of IDPm small interfering RNA on HeLa cells offers the possibility of developing a modifier of radiation therapy. SN - 0021-9258 UR - https://www.unboundmedicine.com/medline/citation/17350954/Regulation_of_ionizing_radiation_induced_apoptosis_by_mitochondrial_NADP+_dependent_isocitrate_dehydrogenase_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0021-9258(17)47415-1 DB - PRIME DP - Unbound Medicine ER -