DRG2 Accelerates Senescence via Negative Regulation of SIRT1 in Human Diploid Fibroblasts

Accumulating evidence suggests that developmentally regulated GTP-binding protein 2 (DRG2), an evolutionarily conserved GTP-binding protein, plays an important role in regulating cell growth, inflammation, and mitochondria dynamics. However, the effect of DRG2 in aging remains unclear. In this study...

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Autores principales:	Bing Si Li, Ai Lin Jin, ZiQi Zhou, Jae Ho Seo, Byung-Min Choi
Formato:	article
Lenguaje:	EN
Publicado:	Hindawi Limited 2021
Materias:	Cytology QH573-671
Acceso en línea:	https://doaj.org/article/b264a996a4ca4be2b007eae02a2c2d4d
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spelling	oai:doaj.org-article:b264a996a4ca4be2b007eae02a2c2d4d2021-11-15T01:19:33ZDRG2 Accelerates Senescence via Negative Regulation of SIRT1 in Human Diploid Fibroblasts1942-099410.1155/2021/7301373https://doaj.org/article/b264a996a4ca4be2b007eae02a2c2d4d2021-01-01T00:00:00Zhttp://dx.doi.org/10.1155/2021/7301373https://doaj.org/toc/1942-0994Accumulating evidence suggests that developmentally regulated GTP-binding protein 2 (DRG2), an evolutionarily conserved GTP-binding protein, plays an important role in regulating cell growth, inflammation, and mitochondria dynamics. However, the effect of DRG2 in aging remains unclear. In this study, we found that endogenous DRG2 protein expression is upregulated in oxidative stress-induced premature senescence models and tissues of aged mice. Ectopic expression of DRG2 significantly promoted senescence-associated β-galactosidase (SA-β-gal) activity and inhibited cell growth, concomitant with increase in levels of acetyl (ac)-p53 (Lys382), ac-nuclear factor-kB (NF-κB) p65 (Lys310), p21Waf1/Cip1, and p16Ink4a and a decrease in cyclin D1. In this process, reactive oxygen species (ROS) and phosphorylation of H2A histone family member X (H2A.X), forming γ-H2A.X, were enhanced. Mechanistically, ectopic expression of DRG2 downregulated Sirtuin-1 (SIRT1), resulting in augmented acetylation of p53 and NF-κB p65. Additionally, DRG2 knockdown significantly abolished oxidative stress-induced premature senescence. Our results provide a possible molecular mechanism for investigation of cellular senescence and aging regulated by DRG2.Bing Si LiAi Lin JinZiQi ZhouJae Ho SeoByung-Min ChoiHindawi LimitedarticleCytologyQH573-671ENOxidative Medicine and Cellular Longevity, Vol 2021 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Cytology QH573-671
spellingShingle	Cytology QH573-671 Bing Si Li Ai Lin Jin ZiQi Zhou Jae Ho Seo Byung-Min Choi DRG2 Accelerates Senescence via Negative Regulation of SIRT1 in Human Diploid Fibroblasts
description	Accumulating evidence suggests that developmentally regulated GTP-binding protein 2 (DRG2), an evolutionarily conserved GTP-binding protein, plays an important role in regulating cell growth, inflammation, and mitochondria dynamics. However, the effect of DRG2 in aging remains unclear. In this study, we found that endogenous DRG2 protein expression is upregulated in oxidative stress-induced premature senescence models and tissues of aged mice. Ectopic expression of DRG2 significantly promoted senescence-associated β-galactosidase (SA-β-gal) activity and inhibited cell growth, concomitant with increase in levels of acetyl (ac)-p53 (Lys382), ac-nuclear factor-kB (NF-κB) p65 (Lys310), p21Waf1/Cip1, and p16Ink4a and a decrease in cyclin D1. In this process, reactive oxygen species (ROS) and phosphorylation of H2A histone family member X (H2A.X), forming γ-H2A.X, were enhanced. Mechanistically, ectopic expression of DRG2 downregulated Sirtuin-1 (SIRT1), resulting in augmented acetylation of p53 and NF-κB p65. Additionally, DRG2 knockdown significantly abolished oxidative stress-induced premature senescence. Our results provide a possible molecular mechanism for investigation of cellular senescence and aging regulated by DRG2.
format	article
author	Bing Si Li Ai Lin Jin ZiQi Zhou Jae Ho Seo Byung-Min Choi
author_facet	Bing Si Li Ai Lin Jin ZiQi Zhou Jae Ho Seo Byung-Min Choi
author_sort	Bing Si Li
title	DRG2 Accelerates Senescence via Negative Regulation of SIRT1 in Human Diploid Fibroblasts
title_short	DRG2 Accelerates Senescence via Negative Regulation of SIRT1 in Human Diploid Fibroblasts
title_full	DRG2 Accelerates Senescence via Negative Regulation of SIRT1 in Human Diploid Fibroblasts
title_fullStr	DRG2 Accelerates Senescence via Negative Regulation of SIRT1 in Human Diploid Fibroblasts
title_full_unstemmed	DRG2 Accelerates Senescence via Negative Regulation of SIRT1 in Human Diploid Fibroblasts
title_sort	drg2 accelerates senescence via negative regulation of sirt1 in human diploid fibroblasts
publisher	Hindawi Limited
publishDate	2021
url	https://doaj.org/article/b264a996a4ca4be2b007eae02a2c2d4d
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DRG2 Accelerates Senescence via Negative Regulation of SIRT1 in Human Diploid Fibroblasts

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