Mechanisms involved in responses to the poroxisome proliferator WY-14,643 on gap junctional intercellular communication in V79 hamster fibroblasts.
WY-14,643, a potent hepatic peroxisome proliferator, decreased gap junctional intercellular communication when used at low and intermediate concentrations (1 nM to 10 microM) in the V79 Chinese hamster fibroblast cell line. It did not decrease intercellular communication in early passage Syrian hamster embryo fibroblasts. The mechanism of WY-14,643-induced suppression of intercellular communication was studied by preexposure of V79 cells to inhibitors of protein kinase C, mitogen-activated protein kinases, phosphatidylinositol 3-kinase, or mammalian target-of-rapamycin before addition of WY-14,643. Only protein kinase C, particularly the delta isoform, appeared involved in the inhibition of communication by WY-14,643. Also clofibrate-induced suppression of GJIC in V79 cells appeared to involve protein kinase Cdelta. Furthermore, WY-14,643 did not cause any activation of the mitogen-activated protein kinases p44/42, p38, or Jun N-terminal kinase. When WY-14,643 was used at a higher concentration (100 microM), intercellular communication was increased both in V79 and Syrian hamster embryo cells. This effect was inhibited by preexposure of V79 cells to brefeldin A. Thus, there may be a pool of connexins in the Golgi complex that could be recruited to the plasma membrane upon exposure to high concentrations of WY-14,643.
Department of Environmental and Occupational Cancer, Institute for Cancer Research, The Norwegian Radium Hospital, N-0310, Oslo, Norway.
Véronique
V
Cruciani
Svein-Ole
SO
Mikalsen
D000098:Acetophenones / Q000494:pharmacology; D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology; D020126:Brefeldin A / Q000494:pharmacology; D002070:Butadienes / Q000494:pharmacology; D002450:Cell Communication / Q000187:drug effects*; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D017629:Gap Junctions / Q000187:drug effects*; D007093:Imidazoles / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D008301:Maleimides / Q000494:pharmacology; D008647:Mesocricetus; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D009570:Nitriles / Q000494:pharmacology; D020025:Peroxisome Proliferators / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*; D020123:Sirolimus / Q000494:pharmacology; D000077191:Wortmannin
D000098:Acetophenones; D000730:Androstadienes; D001578:Benzopyrans; D002070:Butadienes; D004791:Enzyme Inhibitors; D005419:Flavonoids; D007093:Imidazoles; D007211:Indoles; D008301:Maleimides; D009570:Nitriles; D020025:Peroxisome Proliferators; D011500:Protein Synthesis Inhibitors; D011725:Pyridines; D011743:Pyrimidines; C113580:U 0126; D020126:Brefeldin A; C006253:pirinixic acid; C085746:rottlerin; D011493:Protein Kinase C; D020928:Mitogen-Activated Protein Kinases; C070515:bisindolylmaleimide I; C093642:SB 203580; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; D020123:Sirolimus; D000077191:Wortmannin