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Sterol regulatory element-binding protein (SREBP)-1-mediated lipogenesis is involved in cell senescence.

Authors
Kim, YM; Shin, HT; Seo, YH; Byun, HO; Yoon, SH; Lee, IK; Hyun, DH; Chung, HY; Yoon, G
Citation
The Journal of biological chemistry, 285(38):29069-29077, 2010
Journal Title
The Journal of biological chemistry
ISSN
0021-92581083-351X
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 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.
MeSH terms
ATP Citrate (pro-S)-Lyase/geneticsATP Citrate (pro-S)-Lyase/metabolismAnimalsBlotting, WesternCell Aging/drug effectsCell Aging/geneticsCell Aging/physiology*Cell LineCell Membrane/drug effectsCell Membrane/metabolismCells, CulturedChromatography, Thin LayerDeferoxamine/pharmacologyHumansHydrogen Peroxide/pharmacologyLipogenesis/drug effectsLipogenesis/geneticsLipogenesis/physiology*Membrane Lipids/metabolismOrganelles/drug effectsOrganelles/metabolismRNA, Small InterferingRatsRats, Inbred F344Reactive Oxygen Species/metabolismSterol Regulatory Element Binding Protein 1/geneticsSterol Regulatory Element Binding Protein 1/metabolism*
DOI
10.1074/jbc.M110.120386
PMID
20615871
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Biochemistry & Molecular Biology
Journal Papers > School of Medicine / Graduate School of Medicine > Neurosurgery
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윤수한윤계순
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