Document Detail


Hepatic apoptosis postburn is mediated by c-Jun N-terminal kinase 2.
MedLine Citation:
PMID:  23324888     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The trauma of a severe burn injury induces a hypermetabolic response that increases morbidity and mortality. Previously, our group showed that insulin resistance after burn injury is associated with endoplasmic reticulum (ER) stress. Evidence suggests that c-Jun N-terminal kinase (JNK) 2 may be involved in ER stress-induced apoptosis. Here, we hypothesized that JNK2 contributes to the apoptotic response after burn injury downstream of ER stress. To test this, we compared JNK2 knockout mice (-/-) with wild-type mice after inducing a 30% total body surface area thermal injury. Animals were killed after 1, 3, and 5 days. Inflammatory cytokines in the blood were measured by multiplex analysis. Hepatic ER stress and insulin signaling were assessed by Western blotting, and insulin resistance was measured by a peritoneal glucose tolerance test. Apoptosis in the liver was quantified by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining. Liver function was quantified by aspartate aminotransferase and alanine aminotransferase activity assays. Endoplasmic reticulum stress increased after burn in both JNK2 and wild-type mice, indicating that JNK2 activation is downstream of ER stress. Knockout of JNK2 did not affect serum inflammatory cytokines; however, the increase in interleukin 6 mRNA expression was prevented in the knockouts. Serum insulin did not significantly increase in the JNK2 group. On the other hand, insulin signaling (PI3K/Akt pathway) and glucose tolerance tests did not improve in JNK2. As expected, apoptosis in the liver increased after burn injury in wild-type mice but not in JNK2. Aspartate aminotransferase/alanine aminotransferase activity revealed that liver function recovered more quickly in JNK2. This study indicates that JNK2 is a central mediator of hepatic apoptosis after a severe burn.
Authors:
Alexandra H Marshall; Natasha C Brooks; Yaeko Hiyama; Nour Qa'aty; Ahmed Al-Mousawi; Celeste C Finnerty; Marc G Jeschke
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Shock (Augusta, Ga.)     Volume:  39     ISSN:  1540-0514     ISO Abbreviation:  Shock     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-01-17     Completed Date:  2013-06-07     Revised Date:  2014-02-04    
Medline Journal Info:
Nlm Unique ID:  9421564     Medline TA:  Shock     Country:  United States    
Other Details:
Languages:  eng     Pagination:  183-8     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Alanine Transaminase / metabolism
Animals
Apoptosis / physiology*
Aspartate Aminotransferases / metabolism
Burns / enzymology*
Cytokines / metabolism
Endoplasmic Reticulum Stress / physiology*
Insulin / physiology
Insulin Resistance / physiology
Liver Diseases / enzymology*
MAP Kinase Signaling System / physiology
Mice
Mice, Inbred C57BL
Mice, Knockout
Mitogen-Activated Protein Kinase 9 / physiology*
Phosphatidylinositol 3-Kinases / physiology
Grant Support
ID/Acronym/Agency:
GM087285-01/GM/NIGMS NIH HHS; R01 GM087285/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Cytokines; 0/Insulin; EC 2.6.1.1/Aspartate Aminotransferases; EC 2.6.1.2/Alanine Transaminase; EC 2.7.1.-/Phosphatidylinositol 3-Kinases; EC 2.7.1.24/Mitogen-Activated Protein Kinase 9
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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