| Sterol regulatory element-binding protein (SREBP)-1-mediated lipogenesis is involved in cell senescence. | |
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MedLine Citation:
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PMID: 20615871 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Increased cell mass is one of the characteristics of senescent cells, but this event has not been clearly defined. When subcellular organellar mass was estimated with organelle-specific fluorescence dyes, we observed that most membranous organelles progressively increase in mass during cell senescence. This increase was accompanied by an increase in membrane lipids and augmented expression of lipogenic enzymes, such as fatty acid synthase (FAS), ATP citrate lyase, and acetyl-CoA carboxylase. The mature form of sterol regulatory element-binding protein (SREBP)-1 was also elevated. Increased expression of these lipogenic effectors was further observed in the liver tissues of aging Fischer 344 rats. Ectopic expression of mature form of SREBP-1 in both Chang cells and primary young human diploid fibroblasts was enough to induce senescence. Blocking lipogenesis with FAS inhibitors (cerulenin and C75) and via siRNA-mediated silencing of SREBP-1 and ATP citrate lyase significantly attenuated H(2)O(2)-induced senescence. Finally, old human diploid fibroblasts were effectively reversed to young-like cells by challenging with FAS inhibitors. Our results suggest that enhanced lipogenesis is not only a common event, but also critically involved in senescence via SREBP-1 induction, thereby contributing to the increase in organelle mass (as a part of cell mass), a novel indicator of senescence. |
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Authors:
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You-Mie Kim; Hyun-Taek Shin; Yong-Hak Seo; Hae-Ok Byun; Soo-Han Yoon; In-Kyu Lee; Dong-Hoon Hyun; Hae-Young Chung; Gyesoon Yoon |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-07-08 |
Journal Detail:
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Title: The Journal of biological chemistry Volume: 285 ISSN: 1083-351X ISO Abbreviation: J. Biol. Chem. Publication Date: 2010 Sep |
Date Detail:
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Created Date: 2010-09-13 Completed Date: 2010-09-28 Revised Date: 2011-09-20 |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: United States |
Other Details:
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Languages: eng Pagination: 29069-77 Citation Subset: IM |
Affiliation:
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Department of Biochemistry and Molecular Biology, School of Medicine, Ajou University, Suwon 443-721, Korea. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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ATP Citrate (pro-S)-Lyase
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genetics,
metabolism Animals Blotting, Western Cell Aging / drug effects, genetics, physiology* Cell Line Cell Membrane / drug effects, metabolism Cells, Cultured Chromatography, Thin Layer Deferoxamine / pharmacology Humans Hydrogen Peroxide / pharmacology Lipogenesis / drug effects, genetics, physiology* Membrane Lipids / metabolism Organelles / drug effects, metabolism RNA, Small Interfering Rats Rats, Inbred F344 Reactive Oxygen Species / metabolism Sterol Regulatory Element Binding Protein 1 / genetics, metabolism* |
| Chemical | |
Reg. No./Substance:
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0/Membrane Lipids; 0/RNA, Small Interfering; 0/Reactive Oxygen Species; 0/SREBF1 protein, human; 0/Sterol Regulatory Element Binding Protein 1; 70-51-9/Deferoxamine; 7722-84-1/Hydrogen Peroxide; EC 2.3.3.8/ATP Citrate (pro-S)-Lyase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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