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National Institute of Environmental Health Sciences

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Publication Detail

Title: Inhibition of connexin43 gap junctional intercellular communication by TPA requires ERK activation.

Authors: Ruch, R J; Trosko, J E; Madhukar, B V

Published In J Cell Biochem, (2001 Jun 26-Jul 25)

Abstract: The phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA), is a potent inhibitor of gap junctional intercellular communication (GJIC). This inhibition requires activation of protein kinase C (PKC), but the events downstream of this kinase are not known. Since PKC can activate extracellular signal regulated kinases (ERKs) and these also downregulate GJIC, we hypothesized that the inhibition of GJIC by TPA involved ERKs. TPA treatment (10 ng/ml for 30 min) of WB-F344 rat liver epithelial cells strongly activated p42 and p44 ERK-1 and -2, blocked gap junction-mediated fluorescent dye-coupling, and induced connexin43 hyperphosphorylation and gap junction internalization. These effects were completely prevented by inhibitors of PKC (bis-indolylmaleimide I; 2 microM) and ERK activation (U-0126; 10 microM). These data suggest that ERKs are activated by PKC in response to TPA treatment and are downstream mediators of the gap junction effects of the phorbol ester.

PubMed ID: 11500965 Exiting the NIEHS site

MeSH Terms: Animals; Blotting, Western; Cell Communication/drug effects*; Cells, Cultured; Connexin 43/antagonists & inhibitors*; Connexin 43/metabolism; Enzyme Activation/drug effects; Epithelial Cells/cytology; Epithelial Cells/drug effects; Epithelial Cells/enzymology; Epithelial Cells/metabolism; Fluorescent Antibody Technique; Gap Junctions/drug effects*; Gap Junctions/metabolism; Isoquinolines/metabolism; Liver; Mitogen-Activated Protein Kinases/metabolism*; Phosphorylation/drug effects; Protein Kinase C/metabolism; Rats; Tetradecanoylphorbol Acetate/pharmacology*

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