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学科主题: 基础医学
题名:
SIRT1 Overexpression Antagonizes Cellular Senescence with Activated ERK/S6k1 Signaling in Human Diploid Fibroblasts
作者: Huang, Jing1,2; Gan, Qini1,2; Han, Limin1,2; Li, Jian1,2; Zhang, Hai1,2; Sun, Ying1,2; Zhang, Zongyu1,2; Tong, Tanjun1,2
刊名: PLOS ONE
发表日期: 2008-03-05
DOI: 10.1371/journal.pone.0001710
卷: 3, 期:3
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Multidisciplinary Sciences
研究领域[WOS]: Science & Technology - Other Topics
英文摘要:

Sir2, a NAD-dependent deacetylase, modulates lifespan in yeasts, worms and flies. The SIRT1, mammalian homologue of Sir2, regulates signaling for favoring survival in stress. But whether SIRT1 has the function to influence cell viability and senescence under non-stressed conditions in human diploid fibroblasts is far from unknown. Our data showed that enforced SIRT1 expression promoted cell proliferation and antagonized cellular senescence with the characteristic features of delayed Senescence-Associated beta-galactosidase (SA-beta-gal) staining, reduced Senescence-Associated Heterochromatic Foci (SAHF) formation and G1 phase arrest, increased cell growth rate and extended cellular lifespan in human fibroblasts, while dominant-negative SIRT1 allele (H363Y) did not significantly affect cell growth and senescence but displayed a bit decreased lifespan.. Western blot results showed that SIRT1 reduced the expression of p16(INK4A) and promoted phosphorylation of Rb. Our data also exposed that overexpression of SIRT1 was accompanied by enhanced activation of ERK and S6K1 signaling. These effects were mimicked in both WI38 cells and 2BS cells by concentration-dependent resveratrol, a SIRT1 activator. It was noted that treatment of SIRT1-.transfected cells with Rapamycin, a mTOR inhibitor, reduced the phosphorylation of S6K1 and the expression of Id1, implying that SIRT1-induced phosphorylation of S6K1 may be partly for the decreased expression of p16(INK4A) and promoted phosphorylation of Rb in 2BS. It was also observed that the expression of SIRT1 and phosphorylation of ERK and S6K1 was declined in senescent 2BS. These findings suggested that SIRT1-promoted cell proliferation and antagonized cellular senescence in human diploid fibroblasts may be, in part, via the activation of ERK/S6K1 signaling.

语种: 英语
所属项目编号: 2007CB507400 ; 3050082 ; 30671064
项目资助者: National Basic Research Programs of China ; National Natural Science Foundation of China ; National Post doctoral Foundation of China
WOS记录号: WOS:000260586600006
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/63005
Appears in Collections:基础医学院_北京大学衰老研究中心_期刊论文

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作者单位: 1.Peking Univ, Res Ctr Aging, Beijing 100871, Peoples R China
2.Peking Univ Hlth Sci Ctr, Dept Biochem & Mol Biol, Beijing, Peoples R China

Recommended Citation:
Huang, Jing,Gan, Qini,Han, Limin,et al. SIRT1 Overexpression Antagonizes Cellular Senescence with Activated ERK/S6k1 Signaling in Human Diploid Fibroblasts[J]. PLOS ONE,2008,3(3).
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