The effect of surgical treatment following peritoneal sepsis on hepatic gene expression

Roderick A. Barke, Scott Birklid, Rebecca B. Chapin, Sabita Roy, Paul S. Brady, Linda J. Brady

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Abstract

Peritoneal sepsis results in downregulation of the gene that codes for the hepatic mitochondrial enzyme carnitine palmitoyltransferase (CPT). The inhibition of hepatic CPT transcription by sepsis is thought to be mediated, in part, by increased expression of the leucine-zipper DNA transcription factor c-fos. In a cecal ligation and puncture (CLP) model, we examined the temporal effect of surgical treatment (cecal excision) on sepsis-induced inhibition of CPT gene expression. We investigated the hypothesis that Fos protein level will inversely correlate with the regulation of CPT gene expression. Specifically, we studied hepatic Fos nucleoprotein accumulation and CPT gene expression as measured by total mitochondrial CPT activity, CPT protein, and CPT mRNA. We investigated the following groups: (i) CLP followed by cecal excision 6, 12, or 24 hr following initial insult, (ii) concurrent CLP control group, and (iii) concurrent sham CLP reference group. When measured 48 hr following initial surgical insult, we conclude that: (i) in the absence of surgical treatment, peritoneal contamination results in a decrease in hepatic CPT gene expression and an increase in Fos nucleoprotein accumulation; (ii) surgical treatment at 6 or 12 hr following initial insult prevents the downregulation in hepatic CPT gene expression and does not result in Fos nucleoprotein accumulation; and (iii) surgical treatment at 24 hr following insult did not prevent the downregulation of hepatic CPT gene expression and results in an increase in hepatic Fos nucleoprotein accumulation. These data are consistent with the hypothesis that sepsis- induced regulation of hepatic c-fos gene expression, in part, is responsible for the downregulation of CPT gene expression.

Original languageEnglish (US)
Pages (from-to)101-106
Number of pages6
JournalJournal of Surgical Research
Volume60
Issue number1
DOIs
StatePublished - Jan 1 1996
Externally publishedYes

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Carnitine O-Palmitoyltransferase
Sepsis
Gene Expression
Liver
Nucleoproteins
Punctures
Ligation
Therapeutics
Down-Regulation
fos Genes
Leucine Zippers
Proteins

ASJC Scopus subject areas

  • Surgery

Cite this

The effect of surgical treatment following peritoneal sepsis on hepatic gene expression. / Barke, Roderick A.; Birklid, Scott; Chapin, Rebecca B.; Roy, Sabita; Brady, Paul S.; Brady, Linda J.

In: Journal of Surgical Research, Vol. 60, No. 1, 01.01.1996, p. 101-106.

Research output: Contribution to journalArticle

Barke, Roderick A. ; Birklid, Scott ; Chapin, Rebecca B. ; Roy, Sabita ; Brady, Paul S. ; Brady, Linda J. / The effect of surgical treatment following peritoneal sepsis on hepatic gene expression. In: Journal of Surgical Research. 1996 ; Vol. 60, No. 1. pp. 101-106.
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