title: Role of glycogen synthase kinase 3β in protective effect of propofol against hepatic ischemia-reperfusion injury.
abstract: BACKGROUND
  It was previously reported that propofol, an intravenously administered hypnotic and anesthetic agent, protects organs from ischemia-reperfusion (I/R) injury. However, the underlying mechanisms are largely unknown. Glycogen synthase kinase 3β (GSK-3β) is known to play an important role in the oxidative stress-induced apoptosis. In this study, we investigated the role of GSK-3β and mitochondrial permeability transition pore (MPTP) in the protective effects of propofol against hepatic I/R injury.
  
  
  METHODS
  The left and median hepatic artery and the portal vein branches were blocked by no-damage artery clips to create the model of partial ischemia (70%), and liver lobes were subjected to warm ischemia for 30, 60, 90 min, respectively. Reperfusion of 120 min was then initiated by the removal of clamp. The MPTP opening was assessed by measuring mitochondrial large amplitude swelling and mitochondrial membrane potential.
  
  
  RESULTS
  Pretreatment with propofol in conditions of hepatic I/R inhibits the apoptosis of hepatocytes as evidenced by decreased terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells. Importantly, propofol suppressed the mitochondrial GSK-3β by promoting or preserving its phosphorylation at Ser9, thus restraining the opening of MPTP and preventing the mitochondrial swell and mitochondrial membrane potential collapse.
  
  
  CONCLUSIONS
  Propofol protects liver from I/R injury by sustaining the mitochondrial function, which is possibly involved with the modulation of MPTP and GSK-3β.
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, China.
authors.forename: Ge
authors.initials: G
authors.lastname: Zhao
authors.forename: Hongwei
authors.initials: H
authors.lastname: Ma
authors.forename: Xin
authors.initials: X
authors.lastname: Shen
authors.forename: Gao-Feng
authors.initials: GF
authors.lastname: Xu
authors.forename: Yu-Lin
authors.initials: YL
authors.lastname: Zhu
authors.forename: Baoying
authors.initials: B
authors.lastname: Chen
authors.forename: Ru
authors.initials: R
authors.lastname: Tie
authors.forename: Ping
authors.initials: P
authors.lastname: Qu
authors.forename: Yi
authors.initials: Y
authors.lastname: Lv
authors.forename: Haifeng
authors.initials: H
authors.lastname: Zhang
authors.forename: Jun
authors.initials: J
authors.lastname: Yu
mesh_terms: D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology; D051336:Mitochondrial Membranes / Q000187:drug effects / Q000201:enzymology; D018384:Oxidative Stress / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D015742:Propofol / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control*
chemical_list: D018686:Anesthetics, Intravenous; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D038362:Glycogen Synthase Kinase 3; D015742:Propofol
keywords: Apoptosis; Glycogen synthase kinase 3β; Ischemia-reperfusion injury; Liver; Mitochondrial permeability transition pore; Propofol