Superoxide anion release by human endothelial cells: synergism between a phorbol ester and a calcium ionophore.
In order to study the signal transduction mechanism of human endothelial cells (EC), the regulation of superoxide anion (O2-)release in EC has been investigated using the calcium ionophore A23187 and phorbol myristate acetate (PMA), a potential activator of the Ca2+ activated, phospholipid-dependent protein kinase, designated "protein kinase C." PMA enhanced O2- release from EC, and this enhancement occurred regardless of the presence or absence of extracellular Ca2+. A similar increase was produced by A23187; omission of extracellular Ca2+ prevented this increase. Simultaneous stimulation with PMA and A23187 produced a large increase in O2- release at submaximal concentrations of these agents, which, when added separately, caused minimal effects. These findings indicate that the activation of protein kinase C and mobilization of Ca2+ evoked by PMA and A23187 respectively are synergistically effective for eliciting a full physiological response of EC in the generation and release of O2-.
D000838:Anions / Q000378:metabolism; D000001:Calcimycin / Q000494:pharmacology*; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004357:Drug Synergism; D004727:Endothelium / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D009994:Osmolar Concentration; D010704:Phorbols / Q000494:pharmacology*; D013481:Superoxides / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014471:Umbilical Veins / Q000166:cytology / Q000378:metabolism*
D000838:Anions; D010704:Phorbols; D013481:Superoxides; D000001:Calcimycin; D013755:Tetradecanoylphorbol Acetate; D004121:Dimethyl Sulfoxide