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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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Inactivation of Sirtuin2 protects mice from acetaminophen-induced liver injury: possible involvement of ER stress and S6K1 activation

  • Lee, Da Hyun (Brain Korea 21 PLUS Project for Medical Science, Yonsei University) ;
  • Lee, Buhyun (Brain Korea 21 PLUS Project for Medical Science, Yonsei University) ;
  • Park, Jeong Su (Severance Biomedical Science Institute, Yonsei Biomedical Research Institute, Yonsei University College of Medicine) ;
  • Lee, Yu Seol (Brain Korea 21 PLUS Project for Medical Science, Yonsei University) ;
  • Kim, Jin Hee (Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine) ;
  • Cho, Yejin (Severance Biomedical Science Institute, Yonsei Biomedical Research Institute, Yonsei University College of Medicine) ;
  • Jo, Yoonjung (Department of Bioinspired Science, Ewha Womans University) ;
  • Kim, Hyun-Seok (Department of Bioinspired Science, Ewha Womans University) ;
  • Lee, Yong-ho (Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine) ;
  • Nam, Ki Taek (Brain Korea 21 PLUS Project for Medical Science, Yonsei University) ;
  • Bae, Soo Han (Severance Biomedical Science Institute, Yonsei Biomedical Research Institute, Yonsei University College of Medicine)
  • Received : 2018.04.17
  • Accepted : 2018.07.13
  • Published : 2019.03.31
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Abstract

Acetaminophen (APAP) overdose can cause hepatotoxicity by inducing mitochondrial 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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References

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