INCREASED GAP JUNCTIONAL INTERCELLULAR COMMUNICATION IN SYRIAN-HAMSTER EMBRYO CELLS TREATED WITH OXIDATIVE AGENTS

The effects of K2CrO4, H2O2, benzoyl peroxide, menadione, KBrO3 and UV 365nm On gap junctional intercellular communication (GJIC) have been s tudied in the 12-O-tetradecanoylphorbol-13-acetate (TPA)-sensitive Syr ian hamster embryo (SHE) cell line BPNi. All agents were found to incr ease the level of GJIC by 50-100%. Also, in early passage SHE cells, a tendency for increased GJIC was found for the oxidative agents studie d. Hydrogen peroxide was used as a model compound in the subsequent st udies. The increase in GJIC was reversible, and it was not due to an i ncreased nonjunctional permeability. Hydrogen peroxide counteracted th e TPA-induced decrease in GJIC, regardless of whether the cells were e xposed to the compounds simultaneously or the cells were pre-exposed t o TPA before addition of H2O2. The GJIC enhancement by H2O2 was slight ly reduced by the addition of the hydroxyl radical scavenger dimethyls ulphoxide or by the inhibition of catalase by amitrole. The cAMP/prote in kinase A system is the only characterized signal transduction syste m that is known to increase GJIC in most cell types. Hydrogen peroxide did not increase the amount of cAMP (or cGMP) in BPNi cells, while fo rskolin and a phosphodiesterase inhibitor had to increase the cAMP lev el several-fold to affect GJIC to the same degree as the oxidative age nts. Some inhibitors of protein kinase A were assayed for their abilit y to inhibit the increases in GJIC caused by H2O2 and forskolin. Staur osporine inhibited the forskolin-induced increase in GJIC, with much l ess effect on the H2O2-induced increase. H8, H88 and H89 had less effe ct than staurosporine on the forskolin-induced increase in GJIC. The r esults suggest that the cAMP/protein kinase A system may not be involv ed in the increase in GJIC caused by H2O2, although this cannot be com pletely ruled out.