Endothelial eicosanoid metabolism and signal transduction during exposure to oxygen radicals injury.
Several physiological agonists that induce elevation of cytosolic free calcium (Ca2+)-levels act via receptor coupled G-proteins, involving activation of phospholipase C (PLC) and hydrolysis of phosphatidylinositol 4,5-bisphosphate. Activation of the inositol signal transduction pathway that precedes Ca2+ ion mobilization is a well accepted signaling pathway in endothelial cell eicosanoid synthesis. This study was designed to examine possible involvement of phosphoinositides in the effects of oxygen free radicals on Ca2+ liberation and eicosanoid synthesis in human umbilical venous endothelial cells (HUVEC). Hydrogen peroxide (H2O2) was chosen as oxygen radicals generating agent. Stimulation of HUVEC with H2O2 (0.1 mmol/l) led to significant rises in inositol phosphate and diacylglycerol (DAG) levels within 300 seconds and an inhibition of Ca2+ release from internal stores. Eicosanoid formation was detectable despite unchanged levels of cytosolic free Ca2+ and no detectable activation of membrane associated phospholipase A2 (PLA2). This suggests that eicosanoid formation may be mediated through the activation of a Ca2+ independent, cytosolic 40 kDa PLA2 isoenzyme and that DAG could serve as an alternative source for arachidonic acid and seems to sensitize a cytosolic PLA2.
Weigel
G
G
Dept. of Cardiothoracic Surgery, University of Vienna, Austria.
Griesmacher
A
A
Toma
C D
CD
Baecker
C
C
Heinzl
H
H
Mueller
M M
MM
D002478:Cells, Cultured; D015777:Eicosanoids / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000473:pathology; D005609:Free Radicals; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism / Q000633:toxicity*; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction
D015777:Eicosanoids; D005609:Free Radicals; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide