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KMID : 1130220200240040297
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Annals of Geriatric Medicine and Research
2020 Volume.24 No. 4 p.297 ~ p.304
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Sestrin2 Attenuates Cellular Senescence by Inhibiting NADPH Oxidase 4 Expression
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Hwang Chae-Young
Han Ying-Hao
Lee Seung-Min
Cho Sang-Mi
Yu Dae-Yeul
Kwon Ki-Sun
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Abstract
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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.
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KEYWORD
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NOX4, Reactive oxygen species, Senescence, Sestrin2
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