Mitochondrial permeability transition in liver ischemia and reperfusion: role of c-Jun N-terminal kinase 2.

Abstract

The mitochondrial permeability transition (MPT) mediates hepatic necrosis after ischemia and reperfusion (I/R). Here, we studied the role of c-Jun N-terminal kinase 2 (JNK2) in MPT-induced liver injury. Wildtype (WT) and JNK2 knockout (KO) mice underwent 70% liver ischemia for 1 hr followed by reperfusion for 8 hr, after which hepatocyte injury and animal survival was assessed. Compared with WT, JNK2 KO mice had 38% less alanine transaminase release and 39% less necrosis by histology. Survival out to 14 days was also greater in JNK2 KO mice (57% vs. 11%), and overall Kaplan-Meier survival was improved. No difference in apoptosis was observed. Intravital multiphoton microscopy of potential-indicating rhodamine 123 after reperfusion revealed depolarized mitochondria in 82% of WT hepatocytes, which decreased to 43% in JNK2 KO hepatocytes. In conclusion, JNK2 contributes to hepatocellular injury and death after I/R in association with increased mitochondrial dysfunction via the MPT.

• Authors: Tom P Theruvath, Mark C Snoddy, Zhi Zhong, John J Lemasters
• Journal: Transplantation (Transplantation) Vol. 85 Issue 10 Pg. 1500-4 (May 27 2008) ISSN: 0041-1337 [Print] United States
• PMID: 18497693 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Mitogen-Activated Protein Kinase 9
• JNK Mitogen-Activated Protein Kinases

Topics

• Animals
• Apoptosis
• Intracellular Membranes (physiology)
• JNK Mitogen-Activated Protein Kinases (metabolism)
• Mice
• Mice, Knockout
• Mitochondria, Liver (physiology)
• Mitochondrial Membranes (physiology)
• Mitogen-Activated Protein Kinase 9 (deficiency, metabolism)
• Permeability
• Reperfusion Injury (physiopathology)