Sestrin2 Attenuates Cellular Senescence by Inhibiting NADPH Oxidase 4 Expression.
Ann Geriatr Med Res
; 24(4): 297-304, 2020 Dec.
Article
in En
| MEDLINE
| ID: mdl-33227845
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 ß-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)-ß were markedly increased in Sesn2-KO MEFs. Treatment of Sesn2-KO MEFs with the NOX inhibitor diphenyleneiodonium and the TGF-ß inhibitor SB431542 restored cell growth inhibited by Sesn2-KO.CONCLUSION:
Sesn2 attenuates cellular senescence via suppression of TGF-ß- and NOX4-induced reactive oxygen species generation and subsequent inhibition of AMPK.
Full text:
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Collection:
01-internacional
Database:
MEDLINE
Language:
En
Journal:
Ann Geriatr Med Res
Year:
2020
Type:
Article