Effects of peroxisome proliferators and 12-O-tetradecanoyl phorbol-13-acetate on intercellular communication and connexin43 in two hamster fibroblast systems.
Effects of 12-O-tetradecanoyl phorbol 13-acetate (TPA) and the hepatic peroxisome proliferators (HPPs) clofibrate, methyl clofenapate (MCP), di(2-ethylhexyl)phthalate (DEHP) and mono(2-ethylhexyl)phthalate (MEHP) were studied in 2 gap junctional intercellular communication (GJIC) systems, metabolic cooperation in V79 cells and microinjection/dye transfer in Syrian hamster embryo (SHE) cells and V79 cells. TPA inhibited GJIC in both systems but was considerably more potent in V79 cells. SHE cells showed a rapid and transient inhibition of GJIC after exposure to HPPs, with maximal inhibition occurring at 5-15 min. The transient inhibition could be caused by metabolization of the compounds. Clofibrate and MEHP produced strong inhibition of metabolic cooperation in V79 cells at high concentrations, while the effect of MCP and DEHP was lower. However, DEHP, MEHP and clofibrate strongly inhibited dye transfer in V79 cells after a 30 min exposure. Clofibrate also showed a dose- and time-dependent effect on dye transfer in V79 cells. The phosphorylation status of the gap junction protein connexin43 (Cx43) changed minimally in SHE cells after exposure to TPA or HPPs. Cx43 from V79 cells was strongly affected by TPA, but not by HPPs. Immunofluorescence of Cx43 disappeared in both cell types when they were exposed to TPA and MEHP, but not to the other HPPs. Thus, there is no direct correlation between the inhibition of GJIC and changes in the phosphorylation status of Cx43 or the appearance of Cx43 in immunofluorescence experiments. The discrepancies may partly be explained by binding of accessory proteins to Cx43. We point out sequences that may be involved in such binding.
Cruciani
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Centre des Sciences de l'Environnement, Metz, France.
Mikalsen
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Vasseur
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D000818:Animals; D015153:Blotting, Western; D002273:Carcinogens / Q000494:pharmacology*; D002450:Cell Communication / Q000187:drug effects*; D002478:Cells, Cultured; D002992:Clofenapate / Q000494:pharmacology; D002994:Clofibrate / Q000494:pharmacology; D018031:Connexin 43 / Q000032:analysis / Q000378:metabolism*; D006224:Cricetinae; D003412:Cricetulus; D004051:Diethylhexyl Phthalate / Q000031:analogs & derivatives / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects; D017629:Gap Junctions / Q000187:drug effects*; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects; D008168:Lung / Q000166:cytology / Q000187:drug effects*; D008830:Microbodies / Q000187:drug effects*; D010766:Phosphorylation; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D002273:Carcinogens; D018031:Connexin 43; D000960:Hypolipidemic Agents; D002992:Clofenapate; D004051:Diethylhexyl Phthalate; D002994:Clofibrate; D013755:Tetradecanoylphorbol Acetate