Posttranscriptional regulation of connexin 32 expression in liver during acute inflammation.
Gap junctions mediate the communication between adjacent cells in tissues. In the liver, connexin 32 (Cx32) subunits make up the predominating gap junctions. The expression of Cx32 gene has been observed to be down-regulated in response to inflammatory states and during liver regeneration. In the present study we attempt to elucidate the molecular mechanisms underlying the down-regulation of the Cx32 expression during acute inflammation. A decrease in the level of Cx32 mRNA in rat liver occurred between 3 and 6 h after intravenous administration of bacterial lipopolysaccharide (LPS), simultaneously with the induction of an acute inflammatory response characterized by an increase in the level for beta-fibrinogen and a reduction of phosphoenolpyruvate carboxykinase mRNA. The reduction in Cx32 steady-state mRNA levels appears to occur at the posttranscriptional level, since the rate of degradation of this message seems to be higher than the rate of transcription of the gene. Degradation of Cx32 mRNA was blocked by the administration of actinomycin D, but not by cycloheximide, prior to injection of LPS. The stabilization of Cx32 message by actinomycin D correlated with the preservation of Cx32 on the cell surface, which otherwise disappears after administration of LPS alone. These results suggest that cellular communication via gap junctions could be regulated at the level of gene expression, by a posttranscriptional mechanism, during acute inflammatory states.
Gingalewski
C
C
Division of Pediatric Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA.
Wang
K
K
Clemens
M G
MG
De Maio
A
A
D000208:Acute Disease; D000818:Animals; D017630:Connexins / Q000235:genetics* / Q000378:metabolism; D003609:Dactinomycin / Q000494:pharmacology; D015536:Down-Regulation; D005786:Gene Expression Regulation; D006520:Hepatitis, Animal / Q000235:genetics / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008099:Liver / Q000378:metabolism*; D008297:Male; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000097002:Gap Junction beta-1 Protein
D017630:Connexins; D003609:Dactinomycin; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D000097002:Gap Junction beta-1 Protein