Selenium-dependent enzymes in endothelial cell function.
Glutathione peroxidases and thioredoxin reductases are the main selenoproteins expressed by endothelial cells. These enzymes reduce hydroperoxides, their role in endothelial cell physiology, however, by far exceeds prevention of oxidative damage. Reactive oxygen and nitrogen species, especially superoxide, hydroperoxides, and nitric oxide, are crucial signaling molecules in endothelial cells. Their production is regulated by vascular NAD(P)H oxidases and the endothelial nitric oxide synthase. Their metabolism and physiological functions are coordinated by glutathione peroxidases and the thioredoxin/thioredoxin reductase system. Endothelial selenoproteins are involved in the regulation of the vascular tone by maintaining the superoxide anion/nitric oxide balance, of cell adhesion by controlling cell adhesion molecule expression, of apoptosis via inhibition/activation of apoptosis signal-regulating kinase-1, and of eicosanoid production by controlling the activity of cyclooxygenases and lipoxygenases. Accordingly, they regulate inflammatory processes and atherogenesis. The underlying mechanisms are various and differ between individual selenoproteins. Scavenging of hydroperoxides not only prevents oxidative damage, but also interferes with signaling cascades and enzymes involved. Modulation of proteins by hydroperoxide-driven thiol/disulfide exchange is a novel mechanism that needs to be further investigated. A better understanding of the complex interplay of selenoproteins in regulating endothelial cell functions will help to develop a rationale for an improvement of health by an optimum selenium supply.
Brigelius-Flohé
Regina
R
Department of Vitamins and Atherosclerosis, German Institute of Human Nutrition, Arthur-Scheunert-Allee 114-116, D-14558 Bergholz-Rehbrücke, Germany. flohe@mail.dife.de
Banning
Antje
A
Schnurr
Kerstin
K
D000818:Animals; D002318:Cardiovascular Diseases / Q000378:metabolism; D002384:Catalysis; D002448:Cell Adhesion; D015777:Eicosanoids / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D050356:Lipid Metabolism; D008954:Models, Biological; D008956:Models, Chemical; D019255:NADPH Oxidases / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D012643:Selenium / Q000378:metabolism*; D013880:Thioredoxin-Disulfide Reductase / Q000378:metabolism
D015777:Eicosanoids; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; D005979:Glutathione Peroxidase; D019255:NADPH Oxidases; D013880:Thioredoxin-Disulfide Reductase; D012643:Selenium