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

Conference · · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)
OSTI ID:5317587

In order to study the signal transduction mechanism of human endothelial cells (EC), the regulation of superoxide anion (O/sub 2/-) release in EC has been investigated using the calcium ionophore A23187 and phorbol myristate acetate (PMA), a potential activator of the Ca/sup + +/ activated, phospholipid-dependent protein kinase, designated protein kinase C. PMA enhanced O/sub 2/- release from EC in both dose and time-dependent fashion. This enhancement occurred regardless of the presence and absence of extracellular Ca++. A similar increase was produced by A23187. This increase was dependent on the presence of extracellular Ca++, since omission of Ca++ lowered O/sub 2/- release to the control level. Simultaneous stimulation with PMA and A23187 produced a large increase in O/sub 2/- release at submaximal concentrations of these agents. When 0.1 ng/ml PMA and 0.01 ..mu..M A23187 were added simultaneously, the increase in O/sub 2/- release was almost 4 times greater than the sum of the individual increases (rho < 0.01). These findings indicate that the activation of protein kinase C and mobilization of Ca++ evoked by PMA and A23187 respectively are synergistically effective in eliciting a full physiological response of EC in the generation and release of O/sub 2/-.

Research Organization:
Univ. of Texas Health Science Center, Dallas
OSTI ID:
5317587
Report Number(s):
CONF-8604222-
Journal Information:
Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) Vol. 45:3; ISSN FEPRA
Country of Publication:
United States
Language:
English