Sestrin2 attenuates cellular senescence by inhibiting NADPH oxidase 4 expression

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Title
Sestrin2 attenuates cellular senescence by inhibiting NADPH oxidase 4 expression
Author(s)
Chae Young Hwang; Ying Hao Han; Seung-Min LeeSang Mi Cho; Dae Yeul Yu; Ki-Sun Kwon
Bibliographic Citation
Annals of Geriatric Medicine and Research, vol. 24, no. 4, pp. 297-304
Publication Year
2020
Abstract
Background: Sestrin2 (Sesn2) is involved in the maintenance of metabolic homeostasis and aging via modulation of the 5' AMP-activated protein kinase-mammalian target of rapamycin (AMPK-mTOR) pathway. Methods: Wild-type and Sesn2 knockout (KO) mice of the 129/SvJ background were maintained in a pathogen-free authorized facility under a 12-hour dark/light cycle at 20°C?22°C and 50%?60% humidity. Mouse embryonic fibroblasts (MEFs) were prepared from 13.5-day-old embryos derived from Sesn2-KO mice mated with each other. Results: The MEFs from Sesn2-KO mice showed enlarged and flattened morphologies and senescence-associated β-galactosidase activity, accompanied by an elevated level of reactive oxygen species. These senescence phenotypes recovered following treatment with N-acetyl-cysteine. Notably, the mRNA levels of NADPH oxidase 4 (NOX4) and transforming growth factor (TGF)-β were markedly increased in Sesn2-KO MEFs. Treatment of Sesn2-KO MEFs with the NOX inhibitor diphenyleneiodonium and the TGF-β inhibitor SB431542 restored cell growth inhibited by Sesn2-KO. Conclusion: Sesn2 attenuates cellular senescence via suppression of TGF-β- and NOX4-induced reactive oxygen species generation and subsequent inhibition of AMPK.
Keyword
NOX4Reactive oxygen speciesSenescenceSestrin2
ISSN
2508-4798
DOI
http://dx.doi.org/10.4235/agmr.20.0051
Type
Article
Appears in Collections:
Division of Research on National Challenges > Aging Research Center > 1. Journal Articles
Ochang Branch Institute > Division of Bioinfrastructure > Laboratory Animal Resource Center > 1. Journal Articles
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