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

被引:4
作者
Li, Bing Si [1 ]
Jin, Ai Lin [1 ]
Zhou, ZiQi [2 ]
Seo, Jae Ho [1 ,3 ]
Choi, Byung-Min [1 ]
机构
[1] Wonkwang Univ, Sch Med, Dept Biochem, Iksan 54538, Jeonbuk, South Korea
[2] Wonkwang Univ, Sch Korean Med, Dept Herbol, Iksan 54538, Jeonbuk, South Korea
[3] Wonkwang Univ, Sch Med, Sarcopenia Total Solut Ctr, Iksan 54538, Jeonbuk, South Korea
基金
新加坡国家研究基金会;
关键词
CELLULAR SENESCENCE; MOLECULAR-MECHANISMS; OXIDATIVE STRESS; GROWTH ARREST; P53; OVEREXPRESSION; EVOLUTION; CELLS;
D O I
10.1155/2021/7301373
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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 beta-galactosidase (SA-beta-gal) activity and inhibited cell growth, concomitant with increase in levels of acetyl (ac)-p53 (Lys382), ac-nuclear factor-kB (NF-kappa B) p65 (Lys310), p21(Waf1/Cip1), and p16(Ink4a) and a decrease in cyclin D1. In this process, reactive oxygen species (ROS) and phosphorylation of H2A histone family member X (H2A.X), forming gamma-H2A.X, were enhanced. Mechanistically, ectopic expression of DRG2 downregulated Sirtuin-1 (SIRT1), resulting in augmented acetylation of p53 and NF-kappa B 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.
引用
收藏
页数:16
相关论文
共 42 条
[21]   MHY2233 Attenuates Replicative Cellular Senescence in Human Endothelial Progenitor Cells via SIRT1 Signaling [J].
Lamichane, Shreekrishna ;
Baek, Sang Hong ;
Kim, Yeon-Ju ;
Park, Ji Hye ;
Lamichane, Babita Dahal ;
Jang, Woong Bi ;
Ji, SeungTaek ;
Lee, Na Kyung ;
Dehua, Li ;
Kim, Da Yeon ;
Kang, Songhwa ;
Seong, Ha Jong ;
Yun, Jisoo ;
Lee, Dong Hyung ;
Moon, Hyung Ryong ;
Chung, Hae Young ;
Kwon, Sang-Mo .
OXIDATIVE MEDICINE AND CELLULAR LONGEVITY, 2019, 2019
[22]   Human SIR2 deacetylates p53 and antagonizes PML/p53-induced cellular senescence [J].
Langley, E ;
Pearson, M ;
Faretta, M ;
Bauer, UM ;
Frye, RA ;
Minucci, S ;
Pelicci, PG ;
Kouzarides, T .
EMBO JOURNAL, 2002, 21 (10) :2383-2396
[23]   Classification and evolution of P-loop GTPases and related ATPases [J].
Leipe, DD ;
Wolf, YI ;
Koonin, EV ;
Aravind, L .
JOURNAL OF MOLECULAR BIOLOGY, 2002, 317 (01) :41-72
[24]   DRG represents a family of two closely related GTP-binding proteins [J].
Li, B ;
Trueb, B .
BIOCHIMICA ET BIOPHYSICA ACTA-GENE STRUCTURE AND EXPRESSION, 2000, 1491 (1-3) :196-204
[25]   Apigenin Alleviates Oxidative Stress-Induced Cellular Senescence via Modulation of the SIRT1-NAD+-CD38 Axis [J].
Li, Bing Si ;
Zhu, Ri Zhe ;
Lim, Seok-Hee ;
Seo, Jae Ho ;
Choi, Byung-Min .
AMERICAN JOURNAL OF CHINESE MEDICINE, 2021, 49 (05) :1235-1250
[26]   6,4′-dihydroxy-7-methoxyflavanone protects against H2O2-induced cellular senescence by inducing SIRT1 and inhibiting phosphatidylinositol 3-kinase/Akt pathway activation [J].
Li, Bing Si ;
Zhu, Ri Zhe ;
Choi, Byung-Min .
MOLECULAR AND CELLULAR BIOCHEMISTRY, 2021, 476 (02) :863-872
[27]   NF-κB signaling in inflammation [J].
Liu, Ting ;
Zhang, Lingyun ;
Joo, Donghyun ;
Sun, Shao-Cong .
SIGNAL TRANSDUCTION AND TARGETED THERAPY, 2017, 2
[28]   Developmentally regulated GTP-binding protein 2 coordinates Rab5 activity and transferrin recycling [J].
Mani, Muralidharan ;
Lee, Unn Hwa ;
Yoon, Nal Ae ;
Kim, Hyo Jeong ;
Ko, Myoung Seok ;
Seol, Wongi ;
Joe, Yeonsoo ;
Chung, Hun Taeg ;
Lee, Byung Ju ;
Moon, Chang Hoon ;
Cho, Wha Ja ;
Park, Jeong Woo .
MOLECULAR BIOLOGY OF THE CELL, 2016, 27 (02) :334-348
[29]   Cellular response to oxidative stress: Signaling for suicide and survival [J].
Martindale, JL ;
Holbrook, NJ .
JOURNAL OF CELLULAR PHYSIOLOGY, 2002, 192 (01) :1-15
[30]  
Mouchiroud L, 2013, CRIT REV BIOCHEM MOL, V48, P397, DOI 10.3109/10409238.2013.789479