THE EFFECT OF SURGICAL-TREATMENT FOLLOWING PERITONEAL SEPSIS ON HEPATIC GENE-EXPRESSION

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 DN A transcription factor c-fos. In a cecal ligation and puncture (CLP) m odel, we examined the temporal effect of surgical treatment (cecal exc ision) on sepsis-induced inhibition of CPT gene expression. We investi gated the hypothesis that Fos protein level will inversely correlate w ith the regulation of CPT gene expression. Specifically, we studied he patic Fos nucleoprotein accumulation and CPT gene expression as measur ed 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 ab sence of surgical treatment, peritoneal contamination results in a dec rease in hepatic CPT gene expression and an increase in Fos nucleoprot ein accumulation; (ii) surgical treatment at 6 or 12 hr following init ial insult prevents the downregulation in hepatic CPT gene expression and does not result in Fos nucleoprotein accumulation; and (iii) surgi cal treatment at 24 hr following insult did not prevent the downregula tion of hepatic CPT gene expression and results in an increase in hepa tic Pos nucleoprotein accumulation. These data are consistent with the hypothesis that sepsis-induced regulation of hepatic c-fos gene expre ssion, in part, is responsible for the downregulation of CPT gene expr ession. (C) 1996 Academic Press, Inc.