title: Comparative Study on the Cytoprotective Effects of Activated Protein C Treatment in Nonsteatotic and Steatotic Livers under Ischemia-Reperfusion Injury.
abstract: Activated protein C (APC) has cytoprotective effects on liver ischemia-reperfusion injury (IRI). However, it is unclear whether APC is beneficial in steatotic liver IRI. We compared the cytoprotective effects of APC in nonsteatotic and steatotic liver IRI.
  
  
  METHODS
  Mice fed either normal diets (ND mice) or high fat diets (HF mice), were treated with APC or saline (control) and were performed 60 min partial IRI. Moreover, primary steatotic hepatocytes were either untreated or treated with APC and then incubated with H2O2.
  
  
  RESULTS
  APC significantly reduced serum transaminase levels and the inflammatory cells infiltration compared with control at 4 h in ND mice and at 24 h in HF mice. APC inhibited sinusoidal endothelial injury in ND mice, but not in HF mice. In contrast, APC activated adenosine monophosphate-activated protein kinase (AMPK) phosphorylation in HF mice, but not in ND mice. In the in vitro study, APC significantly increased AMPK phosphorylation, ATP concentration, and survival rates of hepatocytes compared with control.
  
  
  CONCLUSIONS
  During IRI in normal liver, APC attenuated initial damage by inhibiting inflammatory cell infiltration and sinusoidal endothelial injury, but not in steatotic liver. However, in steatotic liver, APC might attenuate late damage via activation of AMPK.
authors.affiliation: Department of Hepatobiliary Pancreatic and Transplant Surgery, Mie University Graduate School of Medicine, Edobashi 2-174, Tsu, Mie 514-8507, Japan.
authors.forename: Akitoshi
authors.initials: A
authors.lastname: Matsuda
authors.affiliation: Department of Hepatobiliary Pancreatic and Transplant Surgery, Mie University Graduate School of Medicine, Edobashi 2-174, Tsu, Mie 514-8507, Japan.
authors.forename: Naohisa
authors.initials: N
authors.lastname: Kuriyama
authors.affiliation: Department of Hepatobiliary Pancreatic and Transplant Surgery, Mie University Graduate School of Medicine, Edobashi 2-174, Tsu, Mie 514-8507, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kato
authors.affiliation: Department of Hepatobiliary Pancreatic and Transplant Surgery, Mie University Graduate School of Medicine, Edobashi 2-174, Tsu, Mie 514-8507, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Tanemura
authors.affiliation: Department of Hepatobiliary Pancreatic and Transplant Surgery, Mie University Graduate School of Medicine, Edobashi 2-174, Tsu, Mie 514-8507, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Murata
authors.affiliation: Department of Hepatobiliary Pancreatic and Transplant Surgery, Mie University Graduate School of Medicine, Edobashi 2-174, Tsu, Mie 514-8507, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Azumi
authors.affiliation: Department of Hepatobiliary Pancreatic and Transplant Surgery, Mie University Graduate School of Medicine, Edobashi 2-174, Tsu, Mie 514-8507, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Kishiwada
authors.affiliation: Department of Hepatobiliary Pancreatic and Transplant Surgery, Mie University Graduate School of Medicine, Edobashi 2-174, Tsu, Mie 514-8507, Japan.
authors.forename: Shugo
authors.initials: S
authors.lastname: Mizuno
authors.affiliation: Department of Hepatobiliary Pancreatic and Transplant Surgery, Mie University Graduate School of Medicine, Edobashi 2-174, Tsu, Mie 514-8507, Japan.
authors.forename: Masanobu
authors.initials: M
authors.lastname: Usui
authors.affiliation: Department of Hepatobiliary Pancreatic and Transplant Surgery, Mie University Graduate School of Medicine, Edobashi 2-174, Tsu, Mie 514-8507, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Sakurai
authors.affiliation: Department of Hepatobiliary Pancreatic and Transplant Surgery, Mie University Graduate School of Medicine, Edobashi 2-174, Tsu, Mie 514-8507, Japan.
authors.forename: Shuji
authors.initials: S
authors.lastname: Isaji
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000097:blood*; D000818:Animals; D059305:Diet, High-Fat; D005234:Fatty Liver / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D022781:Hepatocytes / Q000187:drug effects / Q000473:pathology; D006801:Humans; D006861:Hydrogen Peroxide / Q000008:administration & dosage; D008297:Male; D051379:Mice; D011486:Protein C / Q000008:administration & dosage* / Q000378:metabolism; D015427:Reperfusion Injury / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D000637:Transaminases / Q000097:blood
chemical_list: D011486:Protein C; D006861:Hydrogen Peroxide; D000637:Transaminases; D055372:AMP-Activated Protein Kinases