Cytosolic Ca2+movements of endothelial cells exposed to reactive oxygen intermediates: Role of hydroxyl radical-mediated redox alteration of cell-membrane Ca2+channels
- 1 March 1999
- journal article
- Published by Wiley in British Journal of Pharmacology
- Vol. 126 (6), 1462-1470
- https://doi.org/10.1038/sj.bjp.0702438
Abstract
1. The mode of action of reactive oxygen intermediates in cysosolic Ca2+ movements of cultured porcine aortic endothelial cells exposed to xanthine/xanthine oxidase (X/XO) was investigated. 2. Cytosolic Ca2+ movements provoked by X/XO consisted of an initial Ca2+ release from thapsigargin-sensitive intracellular Ca2+ stores and a sustained Ca2+ influx through cell-membrane Ca2+ channels. The Ca2+ movements from both sources were inhibited by catalase, cell-membrane permeable iron chelators (o-phenanthroline and deferoxamine), a *OH scavenger (5,5-dimethyl-1-pyrroline-N-oxide), or an anion channel blocker (disodium 4, 4'-diisothiocyano-2, 2'-stilbenedisulphonic acid), suggesting that *O2- influx through anion channels was responsible for the Ca2+ movements, in which *OH generation catalyzed by intracellular transition metals (i.e., Haber-Weiss cycle) was involved. 3. After an initial Ca2+ elevation provoked by X/XO, cytosolic Ca2+ concentration decreased to a level higher than basal levels. Removal of X/XO slightly enhanced the Ca2+ decrease. Extracellular addition of sulphydryl (SH)-reducing agents, dithiothreitol or glutathione, after the removal of X/XO accelerated the decrement. A Ca2+ channel blocker, Ni2+, abolished the sustained increase in Ca2+, suggesting that Ca2+ influx through cell-membrane Ca2+ channels was extracellularly regulated by the redox state of SH-groups. 4. The X/XO-provoked change in cellular respiration was inhibited by Ni2+ or dithiothreitol as well as inhibitors of Haber-Weiss cycle, suggesting that Ca2+ influx was responsible for *OH-mediated cytotoxicity. We concluded that intracellular *OH generation was involved in the Ca2+ movements in endothelial cells exposed to X/XO. Cytosolic Ca2+ elevation was partly responsible for the oxidants-mediated cytotoxicity.Keywords
This publication has 42 references indexed in Scilit:
- Inhibitory Effect of Lidocaine on Cultured Porcine Aortic Endothelial Cell-dependent Antiaggregation of PlateletsAnesthesiology, 1995
- Effects of H2O2 on Membrane-Potential and [Ca2+]i of Cultured Rat Arterial Smooth Muscle CellsBiochemical and Biophysical Research Communications, 1995
- Inhibitory effect of sevoflurane on nitric oxide release from cultured endothelial cellsEuropean Journal of Pharmacology: Molecular Pharmacology, 1995
- Intracellular oxidative stress induced by nitric oxide synthesis inhibition increases endothelial cell adhesion to neutrophils.Circulation Research, 1994
- Role of intracellular calcium in superoxide-induced hepatocyte injuryHepatology, 1994
- Effects of oxygen free radicals on isolated cardiac myocytes from guinea-pig ventricle: Electrophysiological studiesJournal of Molecular and Cellular Cardiology, 1992
- Regulation of intracellular Mg2+ by superoxide in amnion cellsBiochemical and Biophysical Research Communications, 1992
- Synthesis of a new cell penetrating calpain inhibitor (calpeptin)Biochemical and Biophysical Research Communications, 1988
- Appearance of superoxide anion radical in cerebral extracellular space during increased prostaglandin synthesis in cats.Circulation Research, 1985
- Prevention of granulocyte-mediated oxidant lung injury in rats by a hydroxyl radical scavenger, dimethylthiourea.JCI Insight, 1984