The possible inhibitory role of the leucine-zipper DNA binding protein c-fos in the regulation of hepatic gene expression after sepsis.
BACKGROUND
The leucine-zipper c-fos has been implicated in the regulation of gene expression. We investigated the possible role of c-fos in the regulation of hepatic gene expression after sepsis. Based on previous data demonstrating that sepsis inhibits hepatic gene expression of carnitine palmitoyltransferase (CPT), we hypothesized that c-fos may play a role in the inhibition of CPT gene expression after sepsis.


METHODS
We studied c-fos gene expression after peritoneal sepsis induced by cecal ligation and puncture (CLP) or sham-CLP. To investigate the possible inhibitory role of c-fos on CPT gene transcription, we investigated the effect of c-fos on c-jun-driven CPT promoter-chloramphenicol acyltransferase reporter gene expression in a HepG2 hepatoma cell cotransfection model. To investigate the possible role of cyclic adenosine monophosphate (cAMP) in the regulation of c-fos in vivo, we treated either the sham-CLP group or the CLP group with either vehicle or cAMP.


RESULTS
Peritoneal sepsis in the rat model resulted in a four-fold increase in hepatic c-fos mRNA and c-fos protein. In the cotransfection model, c-fos significantly inhibited c-jun-induced chloramphenicol acyltransferase activity. Treatment with cAMP resulted in a 50% decrease in c-fos protein in either the sham-CLP or CLP group.


CONCLUSIONS
We conclude that (1) sepsis increases hepatic c-fos transcription and translation, (2) c-fos inhibits c-jun-induced CPT gene expression, and (3) cAMP probably does not directly mediate the increase in c-fos after sepsis.
Barke
R A
RA
Department of Surgery, University of Minnesota, Minneapolis.
Brady
P S
PS
Roy
S
S
Charboneau
R
R
Brady
L J
LJ
D000818:Animals; D002334:Carnitine O-Palmitoyltransferase / Q000235:genetics; D000242:Cyclic AMP / Q000502:physiology; D004268:DNA-Binding Proteins / Q000502:physiology*; D005786:Gene Expression Regulation; D007239:Infections / Q000235:genetics*; D016350:Leucine Zippers / Q000235:genetics*; D008099:Liver / Q000503:physiopathology*; D008297:Male; D016760:Proto-Oncogene Proteins c-fos / Q000502:physiology*; D016755:Proto-Oncogene Proteins c-jun / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D015290:Second Messenger Systems / Q000502:physiology; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D000242:Cyclic AMP; D002334:Carnitine O-Palmitoyltransferase