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Shock. 2000 Jul;14(1):53-9.

Interruption of hepatic gap junctional communication in the rat during inflammation induced by bacterial lipopolysaccharide.

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1
Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.

Abstract

Gap junctional cellular communication is important in the propagation of signals that coordinate hepatic metabolism. Hepatocytes express two different connexin (Cx) genes, Cx32 and Cx26, which encode for the subunit component of gap junction channels. Previous studies have shown that the expression of hepatic Cx32 is reduced during inflammatory conditions. The objective of this study was to evaluate whether this decrease in Cx32 expression results in a decrease in hepatic gap junctional communication. Transfer of the dye Lucifer Yellow between hepatocytes was measured after microinjection of single cells in an isolated perfused liver. Livers were harvested from rats subjected to an inflammatory condition induced by administration of bacterial lipopolysaccharide (LPS). A decrease in gap junctional cellular communication was observed within 6 h of the LPS treatment. This decrease in dye coupling was reversible, because gap junctional communication returned to control levels within 48 h of the LPS injection. The inhibition of hepatic gap junctional communication was associated with the disappearance of Cx32 and Cx26 from the hepatocyte plasma membrane as detected by indirect immunostaining. Cx32 mRNA levels were also reduced during inflammation as previously reported. However, Cx26 mRNA levels were unaffected or even transiently increased after the injection of LPS without significant increase in the polypeptide level. Thus, the down-regulation of Cx32 and Cx26 from the hepatocyte surface is apparently due to a rapid degradation of the polypeptide from the cell surface. We hypothesize that this loss of gap junctional cellular communication within the liver may contribute to the disordered hepatic metabolic that occurs during inflammatory states.

PMID:
10909894
[Indexed for MEDLINE]

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