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Sterol Regulatory Element-binding Protein (SREBP)-1-mediated lipogenesis is involved in cell senescence

Title
Sterol Regulatory Element-binding Protein (SREBP)-1-mediated lipogenesis is involved in cell senescence
Authors
Kim Y.-M.Shin H.-T.Seo Y.-H.Byun H.-O.Yoon S.-H.Lee I.-K.Hyun D.-H.Chung H.-Y.Yoon G.
Ewha Authors
현동훈
SCOPUS Author ID
현동훈scopus
Issue Date
2010
Journal Title
Journal of Biological Chemistry
ISSN
0021-9258JCR Link
Citation
vol. 285, no. 38, pp. 29069 - 29077
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
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 H2O2-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. © 2010 by The American Society for Biochemistry and Molecular Biology, Inc.
DOI
10.1074/jbc.M110.120386
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자연과학대학 > 생명과학전공 > Journal papers
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