title: Protective role of silent information regulator 1 against hepatic ischemia: effects on oxidative stress injury, inflammatory response, and MAPKs.
abstract: OBJECTIVE
  Previous studies have verified that silent information regulator 1 (SIRT1), a class III histone deacetylase, protects against ischemia reperfusion (IR) injury (IRI) in some organs. In this study, we examined whether SIRT1 could protect against hepatic IRI and explored the potential mechanisms.
  
  
  METHODS
  We examined whether SIRT1 could protect against hepatic IRI in vivo and in vitro using hepatic-specific SIRT1(-/-) mice, SIRT1 siRNA-transfected hepatocytes and SIRT1(+/+) hepatocytes.
  
  
  RESULTS
  The expression and activity of SIRT1 were significantly reduced during reperfusion compared with that observed in the control group. Hepatic-specific SIRT1(-/-) mice exhibited significant increase of hepatic damage markers and augment of oxidative stress and inflammatory response compared with control mice. In vitro studies demonstrated similar results. Furthermore, SIRT1 upregulation protects against hepatic IRI, through the overexpression of p-JNK, p-p38MAPK, and p-ERK. The protection of SIRT1 can be effectively reversed by the inhibitors of p38MAPK, JNK, and ERK.
  
  
  CONCLUSIONS
  The activation of SIRT1 significantly inhibits the oxidative stress and inflammatory response during hepatic IRI, which can be developed as a novel method to protect against hepatic IRI.
authors: a Department of Cardiovascular Surgery, Xijing Hospital , The Fourth Military Medical University , Xi'an , China.|b Department of Biomedical Engineering , The Fourth Military Medical University , Xi'an , China.
authors: Yang
authors: Y
authors: Yang
authors: c State Key Laboratory of Cancer Biology, Department of Gastroenterology, Xijing Hospital , The Fourth Military Medical University , Xi'an , China.
authors: Song
authors: S
authors: Zhang
authors: d Department of Thoracic Surgery , Tangdu Hospital, The Fourth Military Medical University , Xi'an , China.
authors: Chongxi
authors: C
authors: Fan
authors: a Department of Cardiovascular Surgery, Xijing Hospital , The Fourth Military Medical University , Xi'an , China.
authors: Wei
authors: W
authors: Yi
authors: e Department of Aerospace Medicine , The Fourth Military Medical University , Xi'an , China.
authors: Shuai
authors: S
authors: Jiang
authors: c State Key Laboratory of Cancer Biology, Department of Gastroenterology, Xijing Hospital , The Fourth Military Medical University , Xi'an , China.
authors: Shouyi
authors: S
authors: Di
authors: c State Key Laboratory of Cancer Biology, Department of Gastroenterology, Xijing Hospital , The Fourth Military Medical University , Xi'an , China.
authors: Zhiqiang
authors: Z
authors: Ma
authors: b Department of Biomedical Engineering , The Fourth Military Medical University , Xi'an , China.
authors: Wei
authors: W
authors: Hu
authors: a Department of Cardiovascular Surgery, Xijing Hospital , The Fourth Military Medical University , Xi'an , China.
authors: Chao
authors: C
authors: Deng
authors: b Department of Biomedical Engineering , The Fourth Military Medical University , Xi'an , China.
authors: Jianjun
authors: J
authors: Lv
authors: b Department of Biomedical Engineering , The Fourth Military Medical University , Xi'an , China.
authors: Tian
authors: T
authors: Li
authors: d Department of Thoracic Surgery , Tangdu Hospital, The Fourth Military Medical University , Xi'an , China.
authors: Yongzhan
authors: Y
authors: Nie
authors: a Department of Cardiovascular Surgery, Xijing Hospital , The Fourth Military Medical University , Xi'an , China.
authors: Zhenxiao
authors: Z
authors: Jin
mesh_terms: D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D001219:Aspartate Aminotransferases / Q000378:metabolism; D002460:Cell Line; D022781:Hepatocytes; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008315:Malondialdehyde / Q000378:metabolism; D018345:Mice, Knockout; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D018384:Oxidative Stress; D015427:Reperfusion Injury / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D008315:Malondialdehyde; D007770:L-Lactate Dehydrogenase; D013482:Superoxide Dismutase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D020928:Mitogen-Activated Protein Kinases; D056564:Sirtuin 1
keywords: Silent information regulator 1; hepatic ischemia reperfusion injury; inflammatory response; mitogen-activated protein kinases; oxidative stress injury