Sestrin2 Attenuates Cellular Senescence by Inhibiting NADPH Oxidase 4 Expression
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 pa...
Main Authors: | , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Korea Geriatrics Society
2020-12-01
|
Series: | Annals of Geriatric Medicine and Research |
Subjects: | |
Online Access: | http://www.e-agmr.org/upload/pdf/agmr-20-0051.pdf |
id |
doaj-07b45251ed8e4b5bb8b08789ff54a68a |
---|---|
record_format |
Article |
spelling |
doaj-07b45251ed8e4b5bb8b08789ff54a68a2021-01-05T02:13:08ZengKorea Geriatrics SocietyAnnals of Geriatric Medicine and Research2508-47982508-49092020-12-0124429730410.4235/agmr.20.0051939Sestrin2 Attenuates Cellular Senescence by Inhibiting NADPH Oxidase 4 ExpressionChae Young Hwang0Ying-Hao Han1Seung-Min Lee2Sang-Mi Cho3Dae-Yeul Yu4Ki-Sun Kwon5 Aging Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Korea Aging Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Korea Aging Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Korea Aging Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Korea Aging Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Korea Aging Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, KoreaBackground 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.http://www.e-agmr.org/upload/pdf/agmr-20-0051.pdfnox4reactive oxygen speciessenescencesestrin2 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Chae Young Hwang Ying-Hao Han Seung-Min Lee Sang-Mi Cho Dae-Yeul Yu Ki-Sun Kwon |
spellingShingle |
Chae Young Hwang Ying-Hao Han Seung-Min Lee Sang-Mi Cho Dae-Yeul Yu Ki-Sun Kwon Sestrin2 Attenuates Cellular Senescence by Inhibiting NADPH Oxidase 4 Expression Annals of Geriatric Medicine and Research nox4 reactive oxygen species senescence sestrin2 |
author_facet |
Chae Young Hwang Ying-Hao Han Seung-Min Lee Sang-Mi Cho Dae-Yeul Yu Ki-Sun Kwon |
author_sort |
Chae Young Hwang |
title |
Sestrin2 Attenuates Cellular Senescence by Inhibiting NADPH Oxidase 4 Expression |
title_short |
Sestrin2 Attenuates Cellular Senescence by Inhibiting NADPH Oxidase 4 Expression |
title_full |
Sestrin2 Attenuates Cellular Senescence by Inhibiting NADPH Oxidase 4 Expression |
title_fullStr |
Sestrin2 Attenuates Cellular Senescence by Inhibiting NADPH Oxidase 4 Expression |
title_full_unstemmed |
Sestrin2 Attenuates Cellular Senescence by Inhibiting NADPH Oxidase 4 Expression |
title_sort |
sestrin2 attenuates cellular senescence by inhibiting nadph oxidase 4 expression |
publisher |
Korea Geriatrics Society |
series |
Annals of Geriatric Medicine and Research |
issn |
2508-4798 2508-4909 |
publishDate |
2020-12-01 |
description |
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. |
topic |
nox4 reactive oxygen species senescence sestrin2 |
url |
http://www.e-agmr.org/upload/pdf/agmr-20-0051.pdf |
work_keys_str_mv |
AT chaeyounghwang sestrin2attenuatescellularsenescencebyinhibitingnadphoxidase4expression AT yinghaohan sestrin2attenuatescellularsenescencebyinhibitingnadphoxidase4expression AT seungminlee sestrin2attenuatescellularsenescencebyinhibitingnadphoxidase4expression AT sangmicho sestrin2attenuatescellularsenescencebyinhibitingnadphoxidase4expression AT daeyeulyu sestrin2attenuatescellularsenescencebyinhibitingnadphoxidase4expression AT kisunkwon sestrin2attenuatescellularsenescencebyinhibitingnadphoxidase4expression |
_version_ |
1724348617089613824 |