SIRT3 overexpression antagonizes high glucose accelerated cellular senescence in human diploid fibroblasts via the SIRT3–FOXO1 signaling pathwayReportar como inadecuado




SIRT3 overexpression antagonizes high glucose accelerated cellular senescence in human diploid fibroblasts via the SIRT3–FOXO1 signaling pathway - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

AGE

, Volume 35, Issue 6, pp 2237–2253

First Online: 14 March 2013Received: 12 April 2012Accepted: 18 February 2013

Abstract

Sirtuin 3 SIRT3 is one of the seven mammalian sirtuins, which are homologs of the yeast Sir2 gene. SIRT3 is the only sirtuin reported to be associated with human life span. Many recent studies have indicated that SIRT3 levels are elevated by exercise and caloric restriction, but whether SIRT3 influences cell senescence under stressed conditions in human diploid fibroblasts has not been established. Our data showed that expression of SIRT3 is elevated in human diploid fibroblasts under low glucose 3.3 mM glucose growth conditions and decreased under high glucose 25 mM glucose growth conditions. We have demonstrated that SIRT3 interacts with forkhead box protein O1 FOXO1. High glucose levels also increased aging phenotypes and FOXO1 acetylation level. We have demonstrated that overexpression of SIRT3 under high glucose conditions reduces FOXO1 acetylation, suggesting that deacetylation of FOXO1 by SIRT3 elevates the expression of the FOXO1 target genes, catalase, and manganese superoxide dismutase MnSOD while decreasing senescence phenotypes. We studied the effects of SIRT3 protein knockdown by shRNA under low glucose conditions. The data showed that shRNA-SIRT3 accelerated senescence phenotypes and acetylation of FOXO1; the expression level of catalase and MnSOD decreased compared with the control group. As a consequence, SIRT3 antagonized cellular senescence with the characteristic features of delayed SA-β-gal staining, senescence-associated heterochromatin foci SAHF formation, and p16 expression. These results demonstrate for the first time that SIRT3 overexpression antagonizes high glucose-induced cellular senescence in human diploid fibroblasts via the SIRT3–FOXO1 signaling pathway.

KeywordsSIRT3 FOXO1 Human diploid fibroblasts High glucose Cellular senescence Bin Zhang and Shaoyuan Cui, these authors contributed equally to this work.

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Autor: Bin Zhang - Shaoyuan Cui - Xueyuan Bai - Li Zhuo - Xuefeng Sun - Quan Hong - Bo Fu - Jianzhong Wang - Xiangmei Chen - Gua

Fuente: https://link.springer.com/







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