Sestrin2 Attenuates Cellular Senescence by Inhibiting NADPH Oxidase 4 Expression

Chae Young Hwang; Ying-Hao Han; Seung-Min Lee; Sang-Mi Cho; Dae-Yeul Yu; Ki-Sun Kwon

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저자정보: Chae Young Hwang (Aging Research Center Korea Research Institute of Bioscience and Biotechnology Daejeon Korea) Ying-Hao Han (Aging Research Center Korea Research Institute of Bioscience and Biotechnology Daejeon Korea) Seung-Min Lee (Aging Research Center Korea Research Institute of Bioscience and Biotechnology Daejeon Korea) Sang-Mi Cho (Aging Research Center Korea Research Institute of Bioscience and Biotechnology Daejeon Korea) Dae-Yeul Yu (Aging Research Center Korea Research Institute of Bioscience and Biotechnology Daejeon Korea) Ki-Sun Kwon (Aging Research Center Korea Research Institute of Bioscience and Biotechnology Daejeon Korea)

저널정보: 대한노인병학회 Annals of geriatric medicine and research Annals of geriatric medicine and research Vol.24 No.4

발행연도: 2020.1

수록면: 297 - 304 (8page)

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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.

#NOX4 #Reactive oxygen species #Senescence #Sestrin2

참고문헌 (30)

참고문헌 신청

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Budanov AV / 2004 / Regeneration of peroxiredoxins by p53-regulated sestrins, homologs of bacterial AhpD / Science 304:596~600

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