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Cytosolic NADP(+)-dependent isocitrate dehydrogenase status modulates oxidative damage to cells.
Free Radic Biol Med. 2002 Jun 01; 32(11):1185-96.FR

Abstract

NADPH is an important cofactor in many biosynthesis pathways and the regeneration of reduced glutathione, critically important in cellular defense against oxidative damage. It is mainly produced by glucose 6-phosphate dehydrogenase (G6PD), malic enzyme, and the cytosolic form of NADP(+)-dependent isocitrate dehydrogenase (IDPc). Little information is available about the role of IDPc in antioxidant defense. In this study we investigated the role of IDPc against cytotoxicity induced by oxidative stress by comparing the relative degree of cellular responses in three different NIH3T3 cells with stable transfection with the cDNA for mouse IDPc in sense and antisense orientations, where IDPc activities were 3-4-fold higher and 35% lower, respectively, than that in the parental cells carrying the vector alone. Although the activities of other antioxidant enzymes, such as superoxide dismutase, catalase, glutathione reductase, glutathione peroxidase, and G6PD, were comparable in all transformed cells, the ratio of GSSG to total glutathione was significantly higher in the cells expressing the lower level of IDPc. This finding indicates that IDPc is essential for the efficient glutathione recycling. Upon transient exposure to increasing concentrations of H(2)O(2) or menadione, an intracellular source of free radicals and reactive oxygen species, the cells with low levels of IDPc became more sensitive to oxidative damage by H(2)O(2) or menadione. Lipid peroxidation, oxidative DNA damage, and intracellular peroxide generation were higher in the cell-line expressing the lower level of IDPc. However, the cells with the highly over-expressed IDPc exhibited enhanced resistance against oxidative stress, compared to the control cells. This study provides direct evidence correlating the activities of IDPc and the maintenance of the cellular redox state, suggesting that IDPc plays an important role in cellular defense against oxidative stress.

Authors+Show Affiliations

Department of Biochemistry, College of Natural Sciences, Kyungpook National University, Taegu, South Korea.No 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

12031902

Citation

Lee, Su Min, et al. "Cytosolic NADP(+)-dependent Isocitrate Dehydrogenase Status Modulates Oxidative Damage to Cells." Free Radical Biology & Medicine, vol. 32, no. 11, 2002, pp. 1185-96.
Lee SM, Koh HJ, Park DC, et al. Cytosolic NADP(+)-dependent isocitrate dehydrogenase status modulates oxidative damage to cells. Free Radic Biol Med. 2002;32(11):1185-96.
Lee, S. M., Koh, H. J., Park, D. C., Song, B. J., Huh, T. L., & Park, J. W. (2002). Cytosolic NADP(+)-dependent isocitrate dehydrogenase status modulates oxidative damage to cells. Free Radical Biology & Medicine, 32(11), 1185-96.
Lee SM, et al. Cytosolic NADP(+)-dependent Isocitrate Dehydrogenase Status Modulates Oxidative Damage to Cells. Free Radic Biol Med. 2002 Jun 1;32(11):1185-96. PubMed PMID: 12031902.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cytosolic NADP(+)-dependent isocitrate dehydrogenase status modulates oxidative damage to cells. AU - Lee,Su Min, AU - Koh,Ho-Jin, AU - Park,Dong-Chan, AU - Song,Byoung J, AU - Huh,Tae-Lin, AU - Park,Jeen-Woo, PY - 2002/5/29/pubmed PY - 2002/12/3/medline PY - 2002/5/29/entrez SP - 1185 EP - 96 JF - Free radical biology & medicine JO - Free Radic Biol Med VL - 32 IS - 11 N2 - NADPH is an important cofactor in many biosynthesis pathways and the regeneration of reduced glutathione, critically important in cellular defense against oxidative damage. It is mainly produced by glucose 6-phosphate dehydrogenase (G6PD), malic enzyme, and the cytosolic form of NADP(+)-dependent isocitrate dehydrogenase (IDPc). Little information is available about the role of IDPc in antioxidant defense. In this study we investigated the role of IDPc against cytotoxicity induced by oxidative stress by comparing the relative degree of cellular responses in three different NIH3T3 cells with stable transfection with the cDNA for mouse IDPc in sense and antisense orientations, where IDPc activities were 3-4-fold higher and 35% lower, respectively, than that in the parental cells carrying the vector alone. Although the activities of other antioxidant enzymes, such as superoxide dismutase, catalase, glutathione reductase, glutathione peroxidase, and G6PD, were comparable in all transformed cells, the ratio of GSSG to total glutathione was significantly higher in the cells expressing the lower level of IDPc. This finding indicates that IDPc is essential for the efficient glutathione recycling. Upon transient exposure to increasing concentrations of H(2)O(2) or menadione, an intracellular source of free radicals and reactive oxygen species, the cells with low levels of IDPc became more sensitive to oxidative damage by H(2)O(2) or menadione. Lipid peroxidation, oxidative DNA damage, and intracellular peroxide generation were higher in the cell-line expressing the lower level of IDPc. However, the cells with the highly over-expressed IDPc exhibited enhanced resistance against oxidative stress, compared to the control cells. This study provides direct evidence correlating the activities of IDPc and the maintenance of the cellular redox state, suggesting that IDPc plays an important role in cellular defense against oxidative stress. SN - 0891-5849 UR - https://www.unboundmedicine.com/medline/citation/12031902/Cytosolic_NADP_+__dependent_isocitrate_dehydrogenase_status_modulates_oxidative_damage_to_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0891584902008158 DB - PRIME DP - Unbound Medicine ER -