Albumin permeability across endothelial cell monolayer exposed to reactive oxygen intermediates : Involvement of reversible functional alteration of the cell membrane Ca2+channels

活性酸素種曝露による血管内皮細胞単層膜のアルブミン透過性 : 細胞膜カルシウムチャネルの可逆的な機能変化

Saeki Noboru

This study was designed to test the idea that the redox state of sulfhydryl (SH)-groups in cell-membrane Ca2+ channels plays a pivotal role in Ca2+in flux, which in turn causes an increase in albumin permeability across the cultured monolayer of porcine pulmonary artery endothelial (PPAE) cells exposed to xanthine/xanthine oxidase (X/XO). Albumin permeability as well as the concentration of intracellular Ca2+( [Ca2+]i) was increased by XKO. A Hz02 scavenger (catalase), an iron chelator (o-phenanthroline), and a hydroxyl radical scavenger (dimethyl sulfoxide) inhibited these changes provoked by XKO, in which intracellular iron-catalyzed hydroxyl radical generation was suggested to be involved. The increase in albumin permeability and [Ca2+]i continued once the PPAE cells were exposed to XKO. The [Ca2+]wi as decreased by a Ca2+ channel blocker, Ni2+, while the removal of Ni2+in creased [Ca2+]I again, suggesting the sustained Ca2+ influx through cell-membrane Ca" channels was responsible for the [Ca2+]i elevation. Ni2+f ailed to inhibit albumin permeability sustained after the removal of XKO. In contrast, SH-reducing agents (dithiothreitol and glutathione) inhibited the sustained permeability as well as Ca2+ influx. We concluded that the redox alteration of SH-groups in cell-membrane Ca2+ channels was involved in the increase in albumin permeability after exposure of the endothelial cells to oxidative stress.

Albumin permeability

Reactive oxygen intermediates

Calcium channels

Redox state

Medical sciences [ 490 ]

eng

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広島大学