Selenium inhibits 15-hydroperoxyoctadecadienoic acid-induced intracellular adhesion molecule expression in aortic endothelial cells.
Increased intracellular adhesion molecule 1 (ICAM-1) expression and enhanced monocyte recruitment to the endothelium are critical steps in the early development of atherosclerosis. The 15-lipoxygenase 1 (15-LOX1) pathway can generate several proinflammatory eicosanoids that are known to enhance ICAM-1 expression within the vascular endothelium. Oxidative stress can exacerbate endothelial cell inflammatory responses by modifying arachidonic acid metabolism through the 15-LOX1 pathway. Because selenium (Se) influences the oxidant status of cells and can modify the expression of eicosanoids, we investigated the role of this micronutrient in modifying ICAM-1 expression as a consequence of enhanced 15-LOX1 activity. Se supplementation reduced ICAM-1 expression in bovine aortic endothelial cells, an effect that was reversed with 15-LOX1 overexpression or treatment with exogenous 15-hydroperoxyoctadecadienoic acid (15-HPETE). ICAM-1 expression increased proportionately when intracellular15-HPETE levels were allowed to accumulate. However, changes in intracellular 15-HETE levels did not seem to affect ICAM-1 expression regardless of Se status. Our results indicate that Se supplementation can reduce 15-HPETE-induced expression of ICAM-1 by controlling the intracellular accumulation of this fatty acid hydroperoxide in endothelial cells.
Large Animal Clinical Sciences, Michigan State University, East Lansing, MI 48824, USA. sordillo@msu.edu
Lorraine M
LM
Sordillo
Katie L
KL
Streicher
Isis K
IK
Mullarky
Jeffery C
JC
Gandy
Wendy
W
Trigona
Chris M
CM
Corl
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001093:Arachidonate 15-Lipoxygenase / Q000235:genetics / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects; D004336:Drug Antagonism; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis* / Q000235:genetics; D015289:Leukotrienes / Q000378:metabolism / Q000494:pharmacology; D008054:Lipid Peroxides / Q000378:metabolism / Q000494:pharmacology; D016859:Lipoxygenase Inhibitors; D018384:Oxidative Stress; D012643:Selenium / Q000494:pharmacology*; D014162:Transfection; D015854:Up-Regulation / Q000187:drug effects
D000975:Antioxidants; D015289:Leukotrienes; D008054:Lipid Peroxides; D016859:Lipoxygenase Inhibitors; D018799:Intercellular Adhesion Molecule-1; C025086:15-hydroperoxy-5,8,11,13-eicosatetraenoic acid; D001093:Arachidonate 15-Lipoxygenase; D012643:Selenium