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Role of NADP+-dependent isocitrate dehydrogenase (NADP+-ICDH) on cellular defence against oxidative injury by gamma-rays.
Int J Radiat Biol. 2004 Sep; 80(9):635-42.IJ

Abstract

PURPOSE

To investigate the regulation of NADPH-producing isocitrate dehydrogenase (ICDH) in cytosol (IDPc) and mitochondria (IDPm) upon gamma-ray irradiation, and the roles of IDPc and IDPm in the protection against cellular damage induced by gamma-ray irradiation.

MATERIALS AND METHODS

Changes of IDPc and IDPm proteins upon gamma-ray irradiation to NIH3T3 cells were analysed by immunoblotting. To increase or decrease the expression of IDPc or IDPm, NIH3T3 cells were stably transfected with mouse IDPc or IDPm cDNA in either the sense or the antisense direction. The transfected cells with either increased or decreased IDPc or IDPm were exposed to gamma-rays, and the levels of reactive oxygen species generation, protein oxidation and lipid peroxidation were measured.

RESULTS

Both IDPc and IDPm activities were induced by gamma-ray in NIH3T3 cells. Cells with decreased expression of IDPc or IDPm had elevated reactive oxygen species generation, lipid peroxidation and protein oxidation. Conversely, overproduction of IDPc or IDPm protein partially protected the cells from oxidative damage induced by gamma-ray irradiation.

CONCLUSIONS

The protective role of IDPc and IDPm against gamma-ray-induced cellular damage can be attributed to elevated NADPH, reducing equivalents needed for recycling reduced glutathione in the cytosol and mitochondria. Thus, a primary biological function of the ICDHs may be production of NADPH, which is a prerequisite for some cellular defence systems against oxidative damage.

Authors+Show Affiliations

Department of Genetic Engineering, Kyungpook National University, Daegu 702-701, Korea.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo 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

15586883

Citation

Lee, S H., et al. "Role of NADP+-dependent Isocitrate Dehydrogenase (NADP+-ICDH) On Cellular Defence Against Oxidative Injury By Gamma-rays." International Journal of Radiation Biology, vol. 80, no. 9, 2004, pp. 635-42.
Lee SH, Jo SH, Lee SM, et al. Role of NADP+-dependent isocitrate dehydrogenase (NADP+-ICDH) on cellular defence against oxidative injury by gamma-rays. Int J Radiat Biol. 2004;80(9):635-42.
Lee, S. H., Jo, S. H., Lee, S. M., Koh, H. J., Song, H., Park, J. W., Lee, W. H., & Huh, T. L. (2004). Role of NADP+-dependent isocitrate dehydrogenase (NADP+-ICDH) on cellular defence against oxidative injury by gamma-rays. International Journal of Radiation Biology, 80(9), 635-42.
Lee SH, et al. Role of NADP+-dependent Isocitrate Dehydrogenase (NADP+-ICDH) On Cellular Defence Against Oxidative Injury By Gamma-rays. Int J Radiat Biol. 2004;80(9):635-42. PubMed PMID: 15586883.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Role of NADP+-dependent isocitrate dehydrogenase (NADP+-ICDH) on cellular defence against oxidative injury by gamma-rays. AU - Lee,S H, AU - Jo,S H, AU - Lee,S M, AU - Koh,H J, AU - Song,H, AU - Park,J W, AU - Lee,W H, AU - Huh,T L, PY - 2004/12/14/pubmed PY - 2005/1/5/medline PY - 2004/12/14/entrez SP - 635 EP - 42 JF - International journal of radiation biology JO - Int J Radiat Biol VL - 80 IS - 9 N2 - PURPOSE: To investigate the regulation of NADPH-producing isocitrate dehydrogenase (ICDH) in cytosol (IDPc) and mitochondria (IDPm) upon gamma-ray irradiation, and the roles of IDPc and IDPm in the protection against cellular damage induced by gamma-ray irradiation. MATERIALS AND METHODS: Changes of IDPc and IDPm proteins upon gamma-ray irradiation to NIH3T3 cells were analysed by immunoblotting. To increase or decrease the expression of IDPc or IDPm, NIH3T3 cells were stably transfected with mouse IDPc or IDPm cDNA in either the sense or the antisense direction. The transfected cells with either increased or decreased IDPc or IDPm were exposed to gamma-rays, and the levels of reactive oxygen species generation, protein oxidation and lipid peroxidation were measured. RESULTS: Both IDPc and IDPm activities were induced by gamma-ray in NIH3T3 cells. Cells with decreased expression of IDPc or IDPm had elevated reactive oxygen species generation, lipid peroxidation and protein oxidation. Conversely, overproduction of IDPc or IDPm protein partially protected the cells from oxidative damage induced by gamma-ray irradiation. CONCLUSIONS: The protective role of IDPc and IDPm against gamma-ray-induced cellular damage can be attributed to elevated NADPH, reducing equivalents needed for recycling reduced glutathione in the cytosol and mitochondria. Thus, a primary biological function of the ICDHs may be production of NADPH, which is a prerequisite for some cellular defence systems against oxidative damage. SN - 0955-3002 UR - https://www.unboundmedicine.com/medline/citation/15586883/Role_of_NADP+_dependent_isocitrate_dehydrogenase__NADP+_ICDH__on_cellular_defence_against_oxidative_injury_by_gamma_rays_ L2 - https://www.tandfonline.com/doi/full/10.1080/09553000400007680 DB - PRIME DP - Unbound Medicine ER -