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Inactivation of Sirtuin2 protects mice from acetaminophen-induced liver injury: possible involvement of ER stress and S6K1 activation
- Title
- Inactivation of Sirtuin2 protects mice from acetaminophen-induced liver injury: possible involvement of ER stress and S6K1 activation
- Authors
- Lee, Da Hyun; Lee, Buhyun; Park, Jeong Su; Lee, Yu Seol; Kim, Jin Hee; Cho, Yejin; Jo, Yoonjung; Kim, Hyun-Seok; Lee, Yong-ho; Nam, Ki Taek; Bae, Soo Han
- Ewha Authors
- 김현석
- SCOPUS Author ID
- 김현석
- Issue Date
- 2019
- Journal Title
- BMB REPORTS
- ISSN
- 1976-6696
1976-670X
- Citation
- BMB REPORTS vol. 52, no. 3, pp. 190 - 195
- Keywords
- Acetaminophen; ER stress; Hepatotoxicity; S6K1; Sirtuin2
- Publisher
- KOREAN SOCIETY BIOCHEMISTRY &
MOLECULAR BIOLOGY
- Indexed
- SCIE; SCOPUS; KCI
- Document Type
- Article
- Abstract
- Acetaminophen (APAP) overdose can cause hepatotoxicity by inducing mitochondria! damage and subsequent necrosis in hepatocytes. Sirtuin2 (Sirt2) is an NAD(+)-dependent deacetylase that regulates several biological processes, including hepatic gluconeogenesis, as well as inflammatory pathways. We show that APAP decreases the expression of Sirt2. Moreover, the ablation of Sirt2 attenuates APAP-induced liver injuries, such as oxidative stress and mitochondrial damage in hepatocytes. We found that Sirt2 deficiency alleviates the APAP-mediated endoplasmic reticulum (ER) stress and phosphorylation of the p70 ribosomal S6 kinase 1 (S6K1). Moreover, Sirt2 interacts with and deacetylates S6K1, followed by S6K1 phosphorylation induction. This study elucidates the molecular mechanisms underlying the protective role of Sirt2 inactivation in APAP-induced liver injuries.
- DOI
- 10.5483/BMBRep.2019.52.3.083
- Appears in Collections:
- 일반대학원 > 바이오융합과학과 > Journal papers
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