Superoxide anion release by human endothelial cells: synergy 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 (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
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Related Subjects
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ALKALINE EARTH METAL COMPOUNDS
ANIMAL TISSUES
BIOLOGICAL EFFECTS
BODY
CALCIUM COMPOUNDS
CARCINOGENS
DOSE-RESPONSE RELATIONSHIPS
ENDOTHELIUM
ENZYMES
ESTERS
MASS TRANSFER
ORGANIC COMPOUNDS
PHORBOL ESTERS
PHOSPHORUS-GROUP TRANSFERASES
PHOSPHOTRANSFERASES
RADICALS
SUPEROXIDE RADICALS
SYNERGISM
TIME DEPENDENCE
TISSUES
TRANSFERASES