Peroxynitrite diminishes gap junctional communication: Protection by selenite supplementation

Loss of intercellular communication,ia gap junctions has been correlated wi th progression of cells to a malignant phenotype, Here, me show that peroxy nitrite, a mediator of toxicity in inflammatory processes, diminishes gap j unctional intercellular communication (GJIC) in WB-F344 rat liver epithelia l cells, assayed by the scrape-loading dye-transfer technique as well as by microinjection of a fluorescent dye into single cells, Exposure of culture d cells to a steady-state concentration of peroxynitrite of 1.6 mu M for 4 min or to 3-morpholinosydnonimine (SIN-1) at 0.5 mM strongly diminished GJI C, These concentrations of peroxynitrite or SIN-1 were not cytotoxic. When cells were grown in a medium supplemented with sodium selenite (0.1-1 mu M) for 72 h, substantial protection was afforded against the decrease in GJIC by peroxynitrite, Thus, peroxynitrite can disrupt GJIC, and selenium-conta ining proteins protect.