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The protective effect of moderate hypothermia during intestinal ischemia-reperfusion is associated with modification of hepatic transcription factor activation

Record type: Article

Background/purpose: Moderate hypothermia throughout intestinal ischemia-reperfusion (IIR) injury reduces multiple organ dysfunction. Heat shock proteins (HSPs) have been shown to be protective against ischemia-reperfusion injury, and STAT (Signal Transducers and Activators of Transcription) proteins are pivotal determinants of the cellular response to reperfusion injury. The aim of this study is to investigate the mechanism of hypothermic protection during IIR.
Methods: Adult rats underwent intestinal ischemia-reperfusion (IIR), 60-minute ischemia and 60-minute reperfusion, or sham (120 minutes) at either normothermia or moderate hypothermia. Four groups of animals were studied: (1) normothermic sham (NS), (2) normothermic IIR (NIIR), (3) hypothermic sham (HS), and (4) hypothermic IIR (HIIR). Western blotting measured heat shock protein expression, phosphorylated (p-) and total (T-) hepatic STAT-1 and STAT-3.
Results: There were no differences in expression of HSPs 27, 47, 60, i70, c70, or 90 between any of the experimental groups. NIIR caused a significant increase in p-STAT-1 compared with normothermic sham (P < .05) and a highly significant increase in p-STAT-3 (P < .001), both these increases were completely abolished by moderate hypothermia (P < .01 v NIIR.)
Conclusions: The protective effect of moderate hypothermia on liver is not mediated by HSP expression at this time-point. Hypothermia may act by decreasing hepatic STAT activation, supporting the potential therapeutic role of moderate hypothermia. Modulation of STAT activation may also provide novel therapeutic targets.

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Citation

Parkinson, E.J., Townsend, P.A., Stephanou, A., Latchman, D.S., Eaton, S. and Pierro, A. (2004) The protective effect of moderate hypothermia during intestinal ischemia-reperfusion is associated with modification of hepatic transcription factor activation Journal of Pediatric Surgery, 39, (5), pp. 696-701. (doi:10.1016/j.jpedsurg.2004.01.025).

More information

Published date: 2004
Keywords: ischemia, reperfusion, intestinal, hypothermia, liver, heat shock protein, STAT transcription factor

Identifiers

Local EPrints ID: 24895
URI: http://eprints.soton.ac.uk/id/eprint/24895
ISSN: 0022-3468
PURE UUID: 2f80c68c-f9b5-456c-b002-130f01b147bc

Catalogue record

Date deposited: 06 Apr 2006
Last modified: 17 Jul 2017 16:12

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Contributors

Author: E.J. Parkinson
Author: P.A. Townsend
Author: A. Stephanou
Author: D.S. Latchman
Author: S. Eaton
Author: A. Pierro

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