Stimulation of prostaglandin synthesis by human endothelial cells exposed to hypoxia.
In ischemic organs, arachidonic acid (AA) metabolites and mostly prostaglandins (PGs) have been found to be released in high amounts. The mechanism for this AA metabolism activation and its physiological implications are not clear. Because endothelial cells are an important source of PGs and because they seem to be very rapidly affected by ischemia, we developed an in vitro model where human endothelial cells were submitted to hypoxia. An important specific activation of phospholipase A2 was observed during hypoxia, which was concomitant with a rise in cytosolic calcium concentration. Endothelial cells synthetize in normal conditions as a mean 1.42, 1.00, 7.69, and 26.92 ng/mg proteins of, respectively, PGE2, PGD2, PGF2 alpha, PGI2. An important increase of about five- to ninefold in the synthesis of the four PGs was observed during hypoxia, which followed the same kinetics as the PLA2 activation. This increase in PG synthesis was sensitive to cyclooxygenase inhibitors. During reoxygenation, PG synthesis decreased back to the basal level of resting cells, suggesting that cells were able to recover their homeostasis after hypoxia. These observations indicate that endothelial cells exposed to oxygen deprivation are a major source of PGs and could contribute to the high amounts of PG released in vivo in ischemic organs.
Michiels
C
C
Laboratoire de Biochimie Cellulaire, Facultés Universitaires Notre-Dame de la Paix, Namur, Belgium.
Arnould
T
T
Knott
I
I
Dieu
M
M
Remacle
J
J
D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine / Q000494:pharmacology; D016718:Arachidonic Acid / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002250:Carbon Radioisotopes; D015687:Cell Hypoxia; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007700:Kinetics; D010100:Oxygen / Q000494:pharmacology; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2; D011453:Prostaglandins / Q000096:biosynthesis* / Q000302:isolation & purification; D011796:Quinacrine / Q000494:pharmacology; D013229:Stearic Acids / Q000378:metabolism; D014316:Tritium; D014471:Umbilical Veins; D014700:Verapamil / Q000494:pharmacology
D002250:Carbon Radioisotopes; D011453:Prostaglandins; D013229:Stearic Acids; D014316:Tritium; D016718:Arachidonic Acid; C031183:stearic acid; D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; D014700:Verapamil; D010741:Phospholipases A; D054467:Phospholipases A2; D011796:Quinacrine; D010100:Oxygen; D002118:Calcium; D007213:Indomethacin