| Regulation of replicative senescence by NADP+ -dependent isocitrate dehydrogenase. | |
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MedLine Citation:
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PMID: 16337884 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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In Sup Kil; Tae Lin Huh; Young Sup Lee; You Mie Lee; Jeen-Woo Park |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2005-10-11 |
Journal Detail:
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Title: Free radical biology & medicine Volume: 40 ISSN: 0891-5849 ISO Abbreviation: Free Radic. Biol. Med. Publication Date: 2006 Jan |
Date Detail:
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Created Date: 2005-12-12 Completed Date: 2006-03-16 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 8709159 Medline TA: Free Radic Biol Med Country: United States |
Other Details:
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Languages: eng Pagination: 110-9 Citation Subset: IM |
Affiliation:
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School of Life Sciences and Biotechnology, College of Natural Sciences, Kyungpook National University, Taegu 702-701, Korea. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Aging
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physiology* Cell Aging* Cell Cycle Cells, Cultured Cyclin-Dependent Kinase Inhibitor p21 / metabolism Cytosol / enzymology DNA Damage DNA Replication* Fibroblasts / physiology* Humans Isocitrate Dehydrogenase / genetics, metabolism* Lipid Peroxidation Mitochondria / enzymology Oxidation-Reduction Oxidative Stress* Peroxides / metabolism Tumor Suppressor Protein p53 / metabolism beta-Galactosidase / metabolism |
| Chemical | |
Reg. No./Substance:
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0/CDKN1A protein, human; 0/Cyclin-Dependent Kinase Inhibitor p21; 0/Peroxides; 0/Tumor Suppressor Protein p53; EC 1.1.1.41/Isocitrate Dehydrogenase; EC 1.1.1.42/isocitrate dehydrogenase (NADP+); EC 3.2.1.23/beta-Galactosidase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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