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Ischemia/reperfusion injury in the liver of BALB/c mice activates AP-1 and nuclear factor ?B independently of I?B degradation

Zwacka, Ralf M and Zhang, Yulong and Zhou, Weihong and Halldorson, Jeff and Engelhardt, John F (1998) 'Ischemia/reperfusion injury in the liver of BALB/c mice activates AP-1 and nuclear factor ?B independently of I?B degradation.' Hepatology, 28 (4). pp. 1022-1030. ISSN 0270-9139

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Abstract

For many inherited and acquired hepatic diseases, liver transplantation is the only possible therapeutic strategy. Ischemia/reperfusion (I/R) damage to donor tissue is thought to be one component that may play a role in the decline of posttransplant tissue function and ultimately rejection. The transcription factors, AP-1 and nuclear factor κB (NF-κB), play important roles in the acute cellular responses to tissue damage, as well as the inflammatory phase following I/R. We have found that the DNA binding activity of AP-1 was dramatically increased following warm ischemia at 1 to 3 hours postreperfusion. Induced DNA binding activity was composed of predominately c-Jun and JunD hetero- and homodimers as determined by electrophoretic mobility supershift assays. This increase in AP-1 activity occurred in the absence of significant changes in the steady-state protein levels of c-Jun and JunB. Maximal activation of Jun amino-terminal kinase (JNK) occurred within the 25 to 30 minutes postreperfusion, just before the peak in AP-1 DNA binding. These findings suggest that phosphorylation may play an important role in regulating AP-1 transcriptional complexes. Furthermore, JunD protein levels slightly increased at 3 hours postreperfusion, concordant with changes in AP-1 DNA binding activity. The activation of NF-κB at 1 hour postreperfusion was independent of proteolytic degradation of IκB-α or IκB-β. This activation of NF-κB DNA binding activity in the nucleus was preceded by an increase in tyrosine phosphorylation of IκB-α. These studies suggest that JNK, IκB tyrosine kinase, and JunD are potential targets for therapeutic intervention during liver I/R injury.

Item Type: Article
Uncontrolled Keywords: Liver; Cell Nucleus; Animals; Mice, Inbred BALB C; Mice; Ischemia; Reperfusion Injury; Mitogen-Activated Protein Kinases; JNK Mitogen-Activated Protein Kinases; DNA-Binding Proteins; NF-kappa B; Proto-Oncogene Proteins c-jun; Transcription Factor AP-1; Enzyme Activation; Dimerization; Time Factors; Male; I-kappa B Proteins; Calcium-Calmodulin-Dependent Protein Kinases; NF-KappaB Inhibitor alpha
Subjects: R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Divisions: Faculty of Science and Health
Faculty of Science and Health > Life Sciences, School of
SWORD Depositor: Elements
Depositing User: Elements
Date Deposited: 11 Jul 2017 16:03
Last Modified: 15 Jan 2022 00:34
URI: http://repository.essex.ac.uk/id/eprint/8348

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