Superoxide anion release by human endothelial cells: Synergism between a phorbol ester and a calcium ionophore

✍ Scribed by Tsukasa Matsubara; Morris Ziff

• Publisher: John Wiley and Sons
• Year: 1986
• Tongue: English
• Weight: 461 KB
• Volume: 127
• Category: Article
• ISSN: 0021-9541
• DOI: 10.1002/jcp.1041270203

✦ Synopsis

In order to study the signal transduction mechanism of human endothelial cells (EC), the regulation of superoxide anion (02-)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 0,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 02-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 02-. Superoxide anion (Oz-) is generated and released during the respiratory burst by a variety of cell types. It is associated not only with host defense through microbial killing and tumoricidal activities (