Low magnesium stimulated prostacyclin generation in cultured human endothelial cells.
Prostacyclin, synthesized from arachidonic acid, is a strong vasodilator and the most powerful inhibitor known for platelet aggregation. Magnesium deficiency as a risk factor for cardiovascular diseases was related to imbalance of thromboxane and prostacyclin in the vasculature. In this study, we examined the effect of a low level of magnesium on prostacyclin generation in cultured human umbilical vein endothelial cells by measuring arachidonic acid release, 6-ketoprostaglandin F1alpha (6-keto-PGF1alpha) production, calcium ((45)Ca2+) influx, and activity of phospholipase A2 (PLA2) and cyclooxygenases (COX), which are the two main enzymes that control the synthesis of prostacyclin. We found that lower levels of magnesium in the culture medium induced a time- and dose-dependent increase in arachidonic acid release. Low magnesium also enhanced 6-keto-PGF1alpha production, activated PLA2 and COX, enhanced (45)Ca2+ influx and decreased the remaining arachidonic acid in phospholipids. Our data indicate that the enhanced 6-keto-PGF1alpha production could be due to (1) the stimulated (45)Ca2+ influX resulting in an activation of PLA2, (2) the increased arachidonic acid liberation from the cell phospholipid, and (3) the activated COX activity. The increased prostacyclin production could provide protection against the cardiovascular effect of thromboxane which was increased by magnesium deficiency.
Zhou
Qi
Q
Burnsides Research Laboratory, Department of Veterinary Bioscience, University of Illinois, Urbana, USA.
Zhou
Yi
Y
Liu
Wei
W
Kummerow
Fred A
FA
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D011464:Epoprostenol / Q000378:metabolism*; D006801:Humans; D008274:Magnesium / Q000097:blood*; D008275:Magnesium Deficiency / Q000097:blood*; D054467:Phospholipases A2 / Q000378:metabolism; D010743:Phospholipids / Q000737:chemistry; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism
D010743:Phospholipids; D016718:Arachidonic Acid; D015121:6-Ketoprostaglandin F1 alpha; D011464:Epoprostenol; D011451:Prostaglandin-Endoperoxide Synthases; D054467:Phospholipases A2; D008274:Magnesium; D002118:Calcium