Regulation of the 12-O-tetradecanoyl-phorbol-13-acetate-induced inhibition of intercellular communication.
Effects of the tumor promoter 12-O-tetradecanoyl-phorbol-13-acetate (TPA) and protein kinase C (PKC) inhibitors on cell-cell communication were studied in a normal rat liver cell line, clone 9. Communication was observed and quantitated with microspectofluorometric and image analysis techniques following scrape-loading of the cells with lucifer yellow. Lucifer yellow migrated as far as ten cells away from the scraped edge in control populations. Two minute TPA (25-50 micrograms/ml) treatment inhibited dye movement such that the dye remained mainly in the cells at the cut edge. The TPA-induced inhibition of cell-cell communication could be partially blocked by 15 min treatment of the cell populations with the PKC inhibitors trifluoperazine (30 micrograms/ml), staurosporine (2 x 10(-8) or 2 x 10(-6) M), sangivamycin (15 or 200 microM), or a PKC inhibitor peptide (20 micrograms/ml) scraped in at the same time as lucifer yellow. Normal communication was observed in cultures treated only with PKC inhibitors. Lower concentrations of TPA (50 ng/ml-1 micrograms/ml) used for 2 min did not inhibit dye communication. Our results demonstrate the phorbol ester-induced interruption of cell-cell communication. The inhibition of PKC by inhibitors eliminates the effect of TPA on communication. Our data are consistent with a role of PKC in the control of junctional communication.
Murray
S A
SA
Department of Neurobiology, University of Pittsburgh School of Medicine, Pennsylvania 15261.
Plummer
H K
HK
Leonard
E E
EE
Deshmukh
P
P
D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D002450:Cell Communication / Q000187:drug effects*; D002460:Cell Line; D007091:Image Processing, Computer-Assisted; D007546:Isoquinolines; D008099:Liver / Q000166:cytology / Q000187:drug effects*; D008856:Microscopy, Fluorescence; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000494:pharmacology; D011741:Pyrimidine Nucleosides / Q000494:pharmacology; D011817:Rabbits; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014268:Trifluoperazine / Q000494:pharmacology*
D000470:Alkaloids; D007546:Isoquinolines; D011741:Pyrimidine Nucleosides; C005699:sangivamycin; D014268:Trifluoperazine; C017475:lucifer yellow; D011493:Protein Kinase C; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate