Inactivation of Sirtuin2 protects mice from acetaminophen-induced liver injury: Possible involvement of ER stress and S6K1 activation

Da Hyun Lee, Buhyun Lee, Jeong Su Park, Yu Seol Lee, Jin Hee Kim, Yejin Cho, Yoonjung Jo, Hyun Seok Kim, Yong Ho Lee, Ki Taek Nam, Soo Han Bae

Research output: Contribution to journalArticle

5 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)190-195
Number of pages6
JournalBMB reports
Volume52
Issue number3
DOIs
Publication statusPublished - 2019 Jan 1

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology

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    Lee, D. H., Lee, B., Park, J. S., Lee, Y. S., Kim, J. H., Cho, Y., Jo, Y., Kim, H. S., Lee, Y. H., Nam, K. T., & Bae, S. H. (2019). Inactivation of Sirtuin2 protects mice from acetaminophen-induced liver injury: Possible involvement of ER stress and S6K1 activation. BMB reports, 52(3), 190-195. https://doi.org/10.5483/BMBRep.2019.52.3.083