Hepatic apoptosis postburn is mediated by c-Jun N-terminal kinase 2.

Alexandra H Marshall, Natasha C Brooks, Yaeko Hiyama, Nour Qa'aty, Ahmed Al-Mousawi, Celeste C Finnerty, Marc G Jeschke

Shock (Augusta, Ga.) 2013 Feb

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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.

Citation

Alexandra H Marshall, Natasha C Brooks, Yaeko Hiyama, Nour Qa'aty, Ahmed Al-Mousawi, Celeste C Finnerty, Marc G Jeschke. Hepatic apoptosis postburn is mediated by c-Jun N-terminal kinase 2. Shock (Augusta, Ga.). 2013 Feb;39(2):183-8