Selenium deficiency inhibits prostacyclin release and enhances production of platelet activating factor by human endothelial cells.
Selenium is an essential component of glutathione peroxidase, an enzyme which protects cells against peroxidation and controls concentrations of intracellular peroxides. Since selenium deficiency is clinically associated with an increased degree of atherosclerosis, the effects of selenium deficiency on prostacyclin (PGI2) and platelet activating factor (PAF) production by cultured human umbilical vein endothelial cells (HUVEC) were investigated. In selenium-deficient HUVEC, histamine-induced PGI2 synthesis was significantly decreased when compared to selenium-supplemented HUVEC; in contrast, histamine-induced PAF production was increased by selenium deficiency. Histamine-induced inositol trisphosphate and [Ca2+]i responses and the conversion of PGG2 and PGH2 to PGI2 were not altered by selenium deficiency. However, selenium deficiency decreased the conversion of exogenous arachidonate to PGI2 and markedly suppressed glutathione peroxidase activity. These results suggest that selenium deficiency, by decreasing glutathione peroxidase activity, makes HUVEC susceptible to peroxide-induced inhibition of the cyclooxygenase activity of PGH2 synthase, resulting in decreased PGI2 production. These changes may alter platelet function in vivo and thus play a role in the increased incidence of atherosclerosis reported in selenium-deficient individuals.
Hampel
G
G
Department of Medicine, Cornell University Medical College, New York, NY 10021.
Watanabe
K
K
Weksler
B B
BB
Jaffe
E A
EA
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D011464:Epoprostenol / Q000096:biosynthesis*; D005979:Glutathione Peroxidase / Q000378:metabolism; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D010972:Platelet Activating Factor / Q000096:biosynthesis*; D012643:Selenium / Q000008:administration & dosage / Q000172:deficiency* / Q000494:pharmacology; D013917:Thrombin / Q000494:pharmacology; D014471:Umbilical Veins
D001095:Arachidonic Acids; D010972:Platelet Activating Factor; D016718:Arachidonic Acid; D015121:6-Ketoprostaglandin F1 alpha; D006632:Histamine; D015544:Inositol 1,4,5-Trisphosphate; D011464:Epoprostenol; D005979:Glutathione Peroxidase; D013917:Thrombin; D012643:Selenium; D002118:Calcium