Sharov V S, Briviba K, Sies H
Institut für Physiologische Chemie I, Heinrich-Heine-Universität Düsseldorf, Germany.
IUBMB Life. 1999 Oct;48(4):379-84. doi: 10.1080/713803538.
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.
通过间隙连接的细胞间通讯丧失与细胞向恶性表型的进展相关。在此,我们表明,过氧亚硝酸盐是炎症过程中毒性的介质,通过刮擦加载染料转移技术以及将荧光染料显微注射到单个细胞中进行测定,它会减少WB-F344大鼠肝上皮细胞中的间隙连接细胞间通讯(GJIC)。将培养的细胞暴露于1.6微摩尔的稳态过氧亚硝酸盐浓度下4分钟或暴露于0.5毫摩尔的3-吗啉代-sydnonimine(SIN-1)下会强烈减少GJIC。这些过氧亚硝酸盐或SIN-1的浓度没有细胞毒性。当细胞在补充有亚硒酸钠(0.1 - 1微摩尔)的培养基中生长72小时时,可提供实质性的保护,防止过氧亚硝酸盐导致的GJIC减少。因此,过氧亚硝酸盐可破坏GJIC,而含硒蛋白具有保护作用。