@entity8743 inhibits junctional transfer and upregulates XXXX expression by a protein kinase A-dependent pathway.

@entity8743 @entity1369 @entity44601 @entity288 @entity134 @entity866 @entity6164 @entity13509 @entity291 @entity617 @entity2382
We have been investigating the function and gene expression of connexins by vascular wall cells, especially @entity13509 ( @entity13509 ) in @entity291 aortic endothelial cells (BAEC). In this study, we tested the effects of @entity8743 ( @entity2382 ), a gap junction communication (GJC) blocker on the junctional transfer of Lucifer yellow in BAEC. @entity2382 is a water-soluble derivative of the liquorice-root extract @entity44601 . @entity2382 rapidly abolished dye-transfer in the scrape-load transfer assay (a measure of GJC) in a reversible and dose-dependent fashion. We then asked whether the BAEC might somehow compensate for the loss of junctional communication by altering the expression of connexins. Thus, we treated BAEC with 100 microM @entity2382 in serum free medium and determined the total @entity13509 cellular distribution (immunostaining) and protein content (immunoblotting). Besides changes in distribution, by 6 h, @entity13509 content levels increased to 166% +/- 22% (P < 0.0001) of controls. RNA blot data showed two-three fold increases in @entity13509 message in BAEC after 6 h of @entity2382 treatment, suggesting transcriptional control. Since @entity2382 has structural similarities to @entity288 , we tested both @entity1369 and @entity617 but neither drug increased @entity13509 levels, suggesting that the @entity2382 response was not due to a generalized @entity134 effect. @entity866 inhibited the @entity2382 -induced increase in @entity13509 content, suggesting a role for kinases in the signaling pathway. Further studies with inhibitors indicated that PKA but not @entity6164 was implicated. In summary, @entity2382 blocks junctional communication and modulates @entity13509 expression in BAEC. These results suggest a feedback mechanism for control of connexin expression based on junctional patency.
