Ilimaquinone inhibits gap junctional communication in a connexin isotype-specific manner.
Ilimaquinone (IQ) and brefeldin A (BFA) disrupt the Golgi complex structure and block protein transport to the plasma membrane, and inhibit gap junctional communication. HeLa cells expressing rat connexin26, 32, or 43, or mouse connexin31, 36, 45, or 57, were used to study the response patterns of gap junctional communication (dye transfer) to ilimaquinone, brefeldin, and the potent protein kinase C (PKC) activator 12-O-tetradecanoylphorbol-13-acetate (TPA). 12-O-Tetradecanoylphorbol-13-acetate (followed for 2 h) caused dose- and time-dependent decreases in communication for five of seven connexins, the unresponsive being connexin45 and 57. Brefeldin (followed for 6 h) caused dose- and time-dependent decreases in communication for six of seven connexins, the exception being connexin26. These results are consistent with Golgi-mediated transport to the cell membrane for all connexins except connexin26. In contrast, ilimaquinone (followed for 6 h) caused a rapid (15-30 min) and nearly complete inhibition of dye transfer through connexin43 channels. For the other connexins, there was a slow and weak response for connexin26, 31, and 32, reaching 65-70% of control communication level, while connexin36, 45, and 57 were unresponsive. Thus, among the tested connexins, ilimaquinone has a strong specificity for connexin43, and the mechanism appears independent of the Golgi complex and of protein kinase C.
Cruciani
Véronique
V
Department of Environmental and Occupational Cancer, Institute for Cancer Research, The Norwegian Radium Hospital, NO-0310 Oslo, Norway.
Mikalsen
Svein-Ole
SO
D000818:Animals; D020126:Brefeldin A / Q000494:pharmacology; D002450:Cell Communication / Q000187:drug effects; D000072259:Connexin 26; D018031:Connexin 43 / Q000037:antagonists & inhibitors*; D017630:Connexins / Q000037:antagonists & inhibitors; D017629:Gap Junctions / Q000187:drug effects* / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011809:Quinones / Q000494:pharmacology*; D051381:Rats; D012717:Sesquiterpenes / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D018031:Connexin 43; D017630:Connexins; C000607042:GJB2 protein, human; D011500:Protein Synthesis Inhibitors; D011809:Quinones; D012717:Sesquiterpenes; D000072259:Connexin 26; D020126:Brefeldin A; C467077:ilimaquinone; D013755:Tetradecanoylphorbol Acetate