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 Finnerty, Marc G. Jeschke

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)183-188
Number of pages6
JournalShock
Volume39
Issue number2
DOIs
StatePublished - Feb 2013

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Endoplasmic Reticulum Stress
Phosphotransferases
Apoptosis
Liver
Wounds and Injuries
Insulin
Glucose Tolerance Test
Aspartate Aminotransferases
Alanine Transaminase
Insulin Resistance
Mitogen-Activated Protein Kinase 9
Cytokines
DNA Nucleotidylexotransferase
Body Surface Area
Serum
Phosphatidylinositol 3-Kinases
Knockout Mice
Interleukin-6
Hot Temperature
Western Blotting

Keywords

  • endoplasmic reticulum stress
  • inflammation
  • insulin resistance
  • JNK2
  • Severe burn injury

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine
  • Emergency Medicine

Cite this

Marshall, A. H., Brooks, N. C., Hiyama, Y., Qa'Aty, N., Al-Mousawi, A., Finnerty, C., & Jeschke, M. G. (2013). Hepatic apoptosis postburn is mediated by C-Jun N-terminal kinase 2. Shock, 39(2), 183-188. https://doi.org/10.1097/SHK.0b013e31827f40ab

Hepatic apoptosis postburn is mediated by C-Jun N-terminal kinase 2. / Marshall, Alexandra H.; Brooks, Natasha C.; Hiyama, Yaeko; Qa'Aty, Nour; Al-Mousawi, Ahmed; Finnerty, Celeste; Jeschke, Marc G.

In: Shock, Vol. 39, No. 2, 02.2013, p. 183-188.

Research output: Contribution to journalArticle

Marshall, AH, Brooks, NC, Hiyama, Y, Qa'Aty, N, Al-Mousawi, A, Finnerty, C & Jeschke, MG 2013, 'Hepatic apoptosis postburn is mediated by C-Jun N-terminal kinase 2', Shock, vol. 39, no. 2, pp. 183-188. https://doi.org/10.1097/SHK.0b013e31827f40ab
Marshall AH, Brooks NC, Hiyama Y, Qa'Aty N, Al-Mousawi A, Finnerty C et al. Hepatic apoptosis postburn is mediated by C-Jun N-terminal kinase 2. Shock. 2013 Feb;39(2):183-188. https://doi.org/10.1097/SHK.0b013e31827f40ab
Marshall, Alexandra H. ; Brooks, Natasha C. ; Hiyama, Yaeko ; Qa'Aty, Nour ; Al-Mousawi, Ahmed ; Finnerty, Celeste ; Jeschke, Marc G. / Hepatic apoptosis postburn is mediated by C-Jun N-terminal kinase 2. In: Shock. 2013 ; Vol. 39, No. 2. pp. 183-188.
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abstract = "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.",
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