Effect of drugs affecting synthesis or degradation of connexin on onset or completion of ethylene glycol induced inhibition of intercellular gap junctional communication.
The role of a connexin synthesis and degradation in the onset or completion of the ethylene glycol-induced inhibition of the gap junctional intercellular communication (GJIC) in V79-4 Chinese hamster cell line was studied as a model of an interaction between the cells and a potential tumor promoter. GJIC was assessed on two levels: on the cytophysiological level - the dye coupling method, and on the immunocytochemical level - the immunolabeling of connexin43. The specific activator of connexin synthesis - Dibutyryl cAMP made the onset of the EG-induced inhibition of GJIC slower, but its effect was only temporary. On the other hand it also speeded up the re-establishment of standard values of GJIC after the removal of EG. Although the non-specific inhibitor of protein degradation via proteasomes - leupeptin increased the amount of connexin plaques on cell membranes, its effect on GJIC remained insignificant. The non-specific inhibitors of transcription - actinomycin D and translation - cycloheximide significantly inhibited the re-establishment of the standard values of GJIC after the removal of EG. The results indicate that although the storage of connexins in Golghi complex probably plays the principal role in the control of the gap junctional communication, the extensive changes in GJIC activity depend on the de novo synthesis of connexin per se.
Králík
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Department of Cell Biology; Research Institute of Child Health, Brno, 662 62 Czech Republic. brouci@volny.cz
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D000818:Animals; D003994:Bucladesine / Q000378:metabolism; D002460:Cell Line; D004396:Coloring Agents / Q000494:pharmacology; D018031:Connexin 43 / Q000378:metabolism; D017630:Connexins / Q000096:biosynthesis* / Q000378:metabolism*; D006224:Cricetinae; D000242:Cyclic AMP / Q000378:metabolism; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D019855:Ethylene Glycol / Q000494:pharmacology*; D017629:Gap Junctions / Q000187:drug effects*; D006056:Golgi Apparatus / Q000378:metabolism; D007150:Immunohistochemistry; D011401:Promoter Regions, Genetic; D014176:Protein Biosynthesis; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D013997:Time Factors; D014158:Transcription, Genetic
D004396:Coloring Agents; D018031:Connexin 43; D017630:Connexins; D011500:Protein Synthesis Inhibitors; D003609:Dactinomycin; D003994:Bucladesine; D003513:Cycloheximide; D000242:Cyclic AMP; D019855:Ethylene Glycol