C-Jun N-terminal kinase 2 promotes liver injury via the mitochondrial permeability transition after hemorrhage and resuscitation

Hemorrhagic shock leads to hepatic hypoperfusion and activation of mitogen-activated stress kinases (MAPK) like c-Jun N-terminal kinase (JNK) 1 and 2. Our aim was to determine whether mitochondrial dysfunction leading to
Hemorrhagic shock leads to hepatic hypoperfusion and activation of mitogen-activated stress kinases (MAPK) like c-Jun N-terminal kinase (JNK) 1 and 2. Our aim was to determine whether mitochondrial dysfunction leading to hepatic necrosis and apoptosis after hemorrhage/resuscitation (H/R) was dependent on JNK2. Under pentobarbital anesthesia, wildtype (WT) and JNK2 deficient (KO) mice were hemorrhaged to 30 mm Hg for 3 h and then resuscitated with shed blood plus half the volume of lactated Ringer's solution. Serum alanine aminotransferase (ALT), necrosis, apoptosis and oxidative stress were assessed 6 h after resuscitation. Mitochondrial polarization was assessed by intravital microscopy. After H/R, ALT in WT-mice increased from 130 U/L to 4800 U/L. In KO-mice, ALT after H/R was blunted to 1800 U/l (P < 0.05). Necrosis, caspase-3 activity and ROS were all substantially decreased in KO compared to WT mice after H/R. After sham operation, intravital microscopy revealed punctate mitochondrial staining by rhodamine 123 (Rh123), indicating normal mitochondrial polarization. At 4 h after H/R, Rh123 staining became dim and diffuse in 58% of hepatocytes, indicating depolarization and onset of the mitochondrial permeability transition (MPT). By contrast, KO mice displayed less depolarization after H/R (23%, P < 0.05). In conclusion, JNK2 contributes to MPT-mediated liver injury after H/R.
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Metadaten
Author:Christoph Czerny, Tom Prakash Theruvath, Eduardo N. Maldonado, Mark Lehnert, Ingo Marzi, Zhi Zhong, John J. Lemasters
URN:urn:nbn:de:hebis:30:3-267710
DOI:http://dx.doi.org/10.1155/2012/641982
ISSN:0894-8569
ISSN:1607-8462
Pubmed Id:http://www.ncbi.nlm.nih.gov/pubmed?term=22791932
Parent Title (English):HPB surgery
Publisher:Hindawi
Place of publication:New York, NY
Document Type:Article
Language:English
Date of Publication (online):2012/06/27
Date of first Publication:2012/06/27
Publishing Institution:Univ.-Bibliothek Frankfurt am Main
Release Date:2012/10/12
Volume:2012
Issue:Article ID 641982
Pagenumber:9
First Page:1
Last Page:9
Note:
Copyright © 2012 Christoph Czerny et al. This is an open access article distributed under the   Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 
          
Institutes:Medizin
Dewey Decimal Classification:610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - Namensnennung 3.0

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