Journal
TRANSPLANTATION
Volume 85, Issue 10, Pages 1500-1504Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/TP.0b013e31816fefb5
Keywords
apoptosis; c-Jun N-terminal kinase 2; ischemia/reperfusion; mitochondrial permeability transition; necrosis
Categories
Funding
- NCRR NIH HHS [C06 RR015455, C06 RR 015455] Funding Source: Medline
- NIDDK NIH HHS [DK 70844, R37 DK037034, R01 DK070844, R01 DK073336-02, R56 DK037034, R01 DK037034, R01 DK037034-23, DK 37034, DK 073336, R01 DK073336] Funding Source: Medline
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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 I 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.
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