Regulation of the transcription factor C/EBP alpha following peritoneal sepsis.
The transcription factors C/EBP alpha and C/EBP beta belong to the leucine-zipper C/EBP (CCAAT/enhancer binding protein) family of DNA-binding proteins. C/EBP alpha and C/EBP beta are expressed in the liver and are implicated in the control of transcriptional events following following sepsis. It is hypothesized that inhibition of C/EBP alpha gene expression following sepsis may lead to some of the phenotypic features we recognize as sepsis syndrome such as decreased visceral protein (albumin) synthesis. In this study we demonstrate that C/EBP alpha mRNA accumulation is transiently inhibited 12 hr following peritoneal insult, consistent with previous data. However, we demonstrate that (1) there is increased binding of hepatic nuclear protein to the C/EBP alpha DNA response element 48 hr following insult, (2) a marked increase in C/EBP alpha protein is observed 48 hr following CLP insult compared with no increase in hepatic C/EBP alpha protein at 12 hr postinsult, (3) the increase in hepatic C/EBP alpha protein at 48 hr following cecal ligation and puncture is not associated with an increase in C/EBP alpha mRNA accumulation, (4) the increase in hepatic C/EBP alpha protein is associated with an increase in C/EBP beta protein, and (5) hepatic albumin mRNA accumulation is decreased at 12 and 48 hr following insult and does not correlate with the C/EBP alpha protein synthesis. We conclude that the possible role of the transcription factor C/EBP alpha with respect to decreased albumin gene expression following sepsis must be reevaluated.
Chapin
R B
RB
Department of Surgery, University of Minnesota, Minneapolis, USA.
Roy
S
S
Charboneau
R
R
Cain
K
K
Brady
P S
PS
Brady
L J
LJ
Barke
R A
RA
D000418:Albumins / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D022762:CCAAT-Enhancer-Binding Proteins; D002432:Cecum / Q000293:injuries; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D008099:Liver / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D009841:Oligonucleotides / Q000737:chemistry; D010538:Peritonitis / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000378:metabolism*; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D000418:Albumins; D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D009841:Oligonucleotides; D012333:RNA, Messenger; D014157:Transcription Factors; D004247:DNA