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Regulation of replicative senescence by NADP+ -dependent isocitrate dehydrogenase.
Free Radic Biol Med. 2006 Jan 01; 40(1):110-9.FR

Abstract

The free radical hypothesis of aging postulates that senescence is due to an accumulation of cellular oxidative damage, caused largely by reactive oxygen species that are produced as by-products of normal metabolic processes. Recently, we demonstrated that the control of cytosolic and mitochondrial redox balance and the cellular defense against oxidative damage is one of the primary functions of cytosolic (IDPc) and mitochondrial NADP+ -dependent isocitrate dehydrogenase (IDPm) by supplying NADPH for antioxidant systems. In this paper, we demonstrate that modulation of IDPc or IDPm activity in IMR-90 cells regulates cellular redox status and replicative senescence. When we examined the regulatory role of IDPc and IDPm against the aging process with IMR-90 cells transfected with cDNA for IDPc or IDPm in sense and antisense orientations, a clear inverse relationship was observed between the amount of IDPc or IDPm expressed in target cells and their susceptibility to senescence, which was reflected by changes in replicative potential, cell cycle, senescence-associated beta-galactosidase activity, expression of p21 and p53, and morphology of cells. Furthermore, lipid peroxidation, oxidative DNA damage, and intracellular peroxide generation were higher and cellular redox status shifted to a prooxidant condition in the cell lines expressing the lower level of IDPc or IDPm. The results suggest that IDPc and IDPm play an important regulatory role in cellular defense against oxidative stress and in the senescence of IMR-90 cells.

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 availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

16337884

Citation

Kil, In Sup, et al. "Regulation of Replicative Senescence By NADP+ -dependent Isocitrate Dehydrogenase." Free Radical Biology & Medicine, vol. 40, no. 1, 2006, pp. 110-9.
Kil IS, Huh TL, Lee YS, et al. Regulation of replicative senescence by NADP+ -dependent isocitrate dehydrogenase. Free Radic Biol Med. 2006;40(1):110-9.
Kil, I. S., Huh, T. L., Lee, Y. S., Lee, Y. M., & Park, J. W. (2006). Regulation of replicative senescence by NADP+ -dependent isocitrate dehydrogenase. Free Radical Biology & Medicine, 40(1), 110-9.
Kil IS, et al. Regulation of Replicative Senescence By NADP+ -dependent Isocitrate Dehydrogenase. Free Radic Biol Med. 2006 Jan 1;40(1):110-9. PubMed PMID: 16337884.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Regulation of replicative senescence by NADP+ -dependent isocitrate dehydrogenase. AU - Kil,In Sup, AU - Huh,Tae Lin, AU - Lee,Young Sup, AU - Lee,You Mie, AU - Park,Jeen-Woo, Y1 - 2005/10/11/ PY - 2005/06/13/received PY - 2005/08/11/revised PY - 2005/08/15/accepted PY - 2005/12/13/pubmed PY - 2006/3/17/medline PY - 2005/12/13/entrez SP - 110 EP - 9 JF - Free radical biology & medicine JO - Free Radic Biol Med VL - 40 IS - 1 N2 - The free radical hypothesis of aging postulates that senescence is due to an accumulation of cellular oxidative damage, caused largely by reactive oxygen species that are produced as by-products of normal metabolic processes. Recently, we demonstrated that the control of cytosolic and mitochondrial redox balance and the cellular defense against oxidative damage is one of the primary functions of cytosolic (IDPc) and mitochondrial NADP+ -dependent isocitrate dehydrogenase (IDPm) by supplying NADPH for antioxidant systems. In this paper, we demonstrate that modulation of IDPc or IDPm activity in IMR-90 cells regulates cellular redox status and replicative senescence. When we examined the regulatory role of IDPc and IDPm against the aging process with IMR-90 cells transfected with cDNA for IDPc or IDPm in sense and antisense orientations, a clear inverse relationship was observed between the amount of IDPc or IDPm expressed in target cells and their susceptibility to senescence, which was reflected by changes in replicative potential, cell cycle, senescence-associated beta-galactosidase activity, expression of p21 and p53, and morphology of cells. Furthermore, lipid peroxidation, oxidative DNA damage, and intracellular peroxide generation were higher and cellular redox status shifted to a prooxidant condition in the cell lines expressing the lower level of IDPc or IDPm. The results suggest that IDPc and IDPm play an important regulatory role in cellular defense against oxidative stress and in the senescence of IMR-90 cells. SN - 0891-5849 UR - https://www.unboundmedicine.com/medline/citation/16337884/Regulation_of_replicative_senescence_by_NADP+__dependent_isocitrate_dehydrogenase_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0891-5849(05)00453-3 DB - PRIME DP - Unbound Medicine ER -