TY  - JOUR
A1  - Czerny, Christoph
A1  - Theruvath, Tom Prakash
A1  - Maldonado, Eduardo N.
A1  - Lehnert, Mark
A1  - Marzi, Ingo
A1  - Zhong, Zhi
A1  - Lemasters, John J.
T1  - C-Jun N-terminal kinase 2 promotes liver injury via the mitochondrial permeability transition after hemorrhage and resuscitation
T2  - HPB surgery
N2  - 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.
Y1  - 2012
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/26771
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-267710
SN  - 0894-8569
SN  - 1607-8462
N1  - 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.
VL  - 2012
IS  - Article ID 641982
PB  - Hindawi
CY  - New York, NY
ER  -