Involvement of protein kinase B and mitogen-activated protein kinases in experimental normothermic liver ischaemia-reperfusion injury.

Abstract

BACKGROUND:

This study evaluated the role of protein kinase B (PKB), phosphatidylinositol 3-kinase (PI3-K), Bcl-2-associated death protein (BAD) and mitogen-activated protein kinases (MAPKs) in normothermic ischaemia-reperfusion (IR)-induced apoptosis in rat liver.

METHODS:

Rats were divided into two groups that received either phosphate-buffered saline (control) or the caspase inhibitor Z-Asp-2,6-dichorobenzoyloxymethylketone (Z-Asp-cmk), injected intravenously 2 min before the induction of 120 min of normothermic liver ischaemia. Liver apoptosis was assessed by the terminal deoxyribonucleotidyltransferase-mediated dUTP nick end labelling (TUNEL) method. PI3-K, PKB, BAD and MAPK activities were measured in ischaemic and non-ischaemic lobes at various times after reperfusion.

RESULTS:

The number of TUNEL-positive cells was significantly decreased after pretreatment with Z-Asp-cmk. In controls, PI3-K and PKB activities and BAD phosphorylation were inhibited in ischaemic liver lobes. The MAPKs (extracellular signal-regulated kinases, c-Jun N-terminal kinase and p38) showed different patterns of activation during IR. PKB activity was not modified by pretreatment with Z-Asp-cmk.

CONCLUSION:

Induction of apoptosis during IR liver injury might be triggered by inactivation of the antiapoptotic PI3-K-PKB pathway and activation of the proapoptotic MAPKs.

• Authors: R Cursio, N Filippa, C Miele, E Van Obberghen, J Gugenheim
• Journal: The British journal of surgery (Br J Surg) Vol. 93 Issue 6 Pg. 752-61 (Jun 2006) ISSN: 0007-1323 [Print] England
• PMID: 16671069 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright (c) 2006 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.

Chemical References

• bcl-Associated Death Protein
• Phosphatidylinositol 3-Kinases
• Proto-Oncogene Proteins c-akt
• Mitogen-Activated Protein Kinases

Topics

• Analysis of Variance
• Animals
• Apoptosis
• Blotting, Northern
• Immunoblotting
• Liver (blood supply, enzymology)
• Male
• Mitogen-Activated Protein Kinases (physiology)
• Phosphatidylinositol 3-Kinases (physiology)
• Proto-Oncogene Proteins c-akt (physiology)
• Rats
• Rats, Inbred Lew
• Reperfusion Injury (enzymology, etiology)
• bcl-Associated Death Protein (physiology)