Inactivation of Sirtuin2 protects mice from acetaminophen-induced liver injury: possible involvement of ER stress and S6K1 activation
- 주제(키워드) Acetaminophen , ER stress , Hepatotoxicity , S6K1 , Sirtuin2
- 주제(기타) Biochemistry & Molecular Biology
- 설명문(일반) [Lee, Da Hyun; Lee, Buhyun; Lee, Yu Seol; Nam, Ki Taek] Yonsei Univ, Brain Korea PLUS Project Med Sci 21, 50 Yonsei Ro, Seoul 03722, South Korea; [Lee, Da Hyun; Lee, Buhyun; Park, Jeong Su; Lee, Yu Seol; Cho, Yejin; Nam, Ki Taek; Bae, Soo Han] Yonsei Univ, Severance Biomed Sci Inst, Yonsei Biomed Res Inst, Coll Med, 50 Yonsei Ro, Seoul 03722, South Korea; [Jo, Yoonjung; Kim, Hyun-Seok] Ewha Womans Univ, Dept Bioinspired Sci, Seoul 120750, South Korea; [Lee, Yong-ho] Yonsei Univ, Dept Internal Med, Div Endocrinol & Metab, Coll Med, 50-1 Yonsei Ro, Seoul 03722, South Korea; [Lee, Yong-ho] Yonsei Univ, Inst Endocrine Res, Coll Med, 50-1 Yonsei Ro, Seoul 03722, South Korea; [Kim, Jin Hee] Yonsei Univ, Brain Korea PLUS Project Med Sci 21, Coll Med, 50-1 Yonsei Ro, Seoul 03722, South Korea
- 등재 SCIE, SCOPUS, KCI등재
- OA유형 Green Submitted, Green Published, gold
- 발행기관 KOREAN SOCIETY BIOCHEMISTRY & MOLECULAR BIOLOGY
- 발행년도 2019
- URI http://www.dcollection.net/handler/ewha/000000160260
- 본문언어 영어
- Published As http://dx.doi.org/10.5483/BMBRep.2019.52.3.083
- PubMed https://pubmed.ncbi.nlm.nih.gov/30021675
초록/요약
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.
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