Previous studies showed that the expression of connexin 32 (Cx32), the polypeptide subunit component of the major hepatic gap junction, is reduced in liver by changes in mRNA stability during bacterial lipopolysaccharide (LPS)-induced inflammation. In this study, we examined the distribution of Cx32 mRNA poly(A) tail lengths during LPS-induced inflammation, because this is considered the first step in the degradation of many mRNAs. During LPS treatment the first detectable change in Cx32 mRNA was a gradual shortening of its poly(A) tail, which reached a final size of ~20 nucleotides. However, the poly(A) tail did not disappear entirely before the bulk of Cx32 mRNA was degraded. Treatment with actinomycin D, which blocks the degradation of Cx32 mRNA after LPS administration, resulted in the appearance of a completely deadenylated mRNA, which otherwise could not be detected. On the contrary, treatment with cycloheximide resulted in a decrease in the stability of Cx32 mRNA without an apparent change of the poly(A) tail size. The effect of cycloheximide on Cx32 mRNA stability seems to be due indirectly to the induction of an inflammatory response by this drug. These results suggest that, similar for many mRNAs, shortening of the poly(A) tail is one of the first steps in the degradation of Cx32 mRNA during inflammation.

gap junctions; cellular communication; connexins; endotoxin; hepatocytes; mRNA stability; gene regulation

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