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.

MATERIALS AND 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: Ge Zhao, Hongwei Ma, Xin Shen, Gao-Feng Xu, Yu-Lin Zhu, Baoying Chen, Ru Tie, Ping Qu, Yi Lv, Haifeng Zhang, Jun Yu
• Journal: The Journal of surgical research (J Surg Res) Vol. 185 Issue 1 Pg. 388-98 (Nov 2013) ISSN: 1095-8673 [Electronic] United States
• PMID: 23743186 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Inc. All rights reserved.

Chemical References

• Anesthetics, Intravenous
• Glycogen Synthase Kinase 3 beta
• Gsk3b protein, rat
• Glycogen Synthase Kinase 3
• Propofol

Topics

• Anesthetics, Intravenous (pharmacology)
• Animals
• Apoptosis (drug effects)
• Glycogen Synthase Kinase 3 (metabolism)
• Glycogen Synthase Kinase 3 beta
• Liver (drug effects, enzymology, pathology)
• Male
• Mitochondria (drug effects, enzymology)
• Mitochondrial Membranes (drug effects, enzymology)
• Oxidative Stress (drug effects)
• Phosphorylation (drug effects)
• Propofol (pharmacology)
• Random Allocation
• Rats
• Rats, Sprague-Dawley
• Reperfusion Injury (metabolism, pathology, prevention & control)