Peroxynitrite diminishes gap junctional communication: protection by selenite supplementation.
Loss of intercellular communication via gap junctions has been correlated with progression of cells to a malignant phenotype. Here, we show that peroxynitrite, a mediator of toxicity in inflammatory processes, diminishes gap junctional intercellular communication (GJIC) in WB-F344 rat liver epithelial cells, assayed by the scrapeloading dye-transfer technique as well as by microinjection of a fluorescent dye into single cells. Exposure of cultured cells to a steady-state concentration of peroxynitrite of 1.6 microM for 4 min or to 3-morpholinosydnonimine (SIN-1) at 0.5 mM strongly diminished GJIC. These concentrations of peroxynitrite or SIN-1 were not cytotoxic. When cells were grown in a medium supplemented with sodium selenite (0.1-1 microM) for 72 h, substantial protection was afforded against the decrease in GJIC by peroxynitrite. Thus, peroxynitrite can disrupt GJIC, and selenium-containing proteins protect.
Sharov
V S
VS
Institut für Physiologische Chemie I, Heinrich-Heine-Universität Düsseldorf, Germany.
Briviba
K
K
Sies
H
H
D000818:Animals; D002450:Cell Communication / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D003470:Culture Media; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D017629:Gap Junctions / Q000187:drug effects*; D005979:Glutathione Peroxidase / Q000096:biosynthesis; D006706:Homeostasis / Q000187:drug effects; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009566:Nitrates / Q000633:toxicity*; D016877:Oxidants / Q000633:toxicity*; D014176:Protein Biosynthesis; D011506:Proteins; D051381:Rats; D011916:Rats, Inbred F344; D051140:Selenoproteins; D018038:Sodium Selenite / Q000378:metabolism / Q000494:pharmacology*
D003470:Culture Media; D009566:Nitrates; D016877:Oxidants; D011506:Proteins; D051140:Selenoproteins; C039642:peroxynitric acid; D005979:Glutathione Peroxidase; D018038:Sodium Selenite