HEPATIC APOPTOSIS POST-BURN IS MEDIATED BY C-JUN N-TERMINAL KINASE-2
| Autor: | Marc G. Jeschke, Yaeko Hiyama, Natasha C. Brooks, Alexandra H. Marshall, Ahmed M. Al-Mousawi, Celeste C. Finnerty, Nour Qa'aty |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
medicine.medical_specialty
MAP Kinase Signaling System medicine.medical_treatment Apoptosis Critical Care and Intensive Care Medicine Article Mice Phosphatidylinositol 3-Kinases Insulin resistance Internal medicine medicine Animals Insulin Mitogen-Activated Protein Kinase 9 Aspartate Aminotransferases Mice Knockout Glucose tolerance test biology medicine.diagnostic_test Liver Diseases c-jun Alanine Transaminase medicine.disease Endoplasmic Reticulum Stress Mice Inbred C57BL Insulin receptor Endocrinology Alanine transaminase Emergency Medicine biology.protein Unfolded protein response Cytokines Liver function Insulin Resistance Burns |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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