Selenium-Dependent Enzymes in Endothelial Cell Function

Abstract

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.

The role of oxidative stress in the pathophysiology of hypertension

“…135 The antioxidant properties of selenium have been documented in several trials. 134,[136][137][138][139][140][141] At low doses, selenium can provide significant protection of the human coronary artery endothelium against oxidative stress-mediated damage. 133 In an animal model, dietary supplementation with selenium was associated with low levels of cardiac oxidative damage and increased antioxidant expression, as well as a reduction in disease severity and mortality in spontaneously hypertensive rats.…”

Dietary manipulation in musculoskeletal conditions

“…Functions of selenium relevant to RA and OA The potential of selenium to affect RA can be understood from the following Se-associated effects: -Antioxidant selenoenzymes, such as glutathione peroxidise (GPx) reduce lipid hydroperoxides (or H 2 O 2 ) to harmless alcohols (or H 2 O) thus reducing oxidative stress [74]. -GPxs can modulate the production of biologically active eicosanoids by the COX and LOX pathways [74].…”

“…-GPxs can modulate the production of biologically active eicosanoids by the COX and LOX pathways [74]. -Se down-regulates the expression of inflammatory genes [75].…”

The Impact of Senile Cataract Maturity on Blood Oxidative Stress Markers and Glutathione-Dependent Antioxidants: Relations with Lens Variables

“…The majority of blood hydroperoxides are, however, reduced by plasma GPx, and their efficient removal would thus diminish plasma MDA levels as well, as indicated in our study by the significant inverse correlations between plasma GPx, hydroperoxides and MDA. Plasma GPx also expresses a peroxynitrite reductase activity, with implications on redox-signaling and the regulation of vascular tonus (12), which may explain the tendency of SC patients with HTA to have lower plasma GPx than the normotensive ones. In comparison to immature SC, plasma GPx and GR acti vities were markedly decreased in the mature SC group, with GR activity independently associated with the severity of disease [OR 5.14 (CI 1.82-14.51); p=0.0020].…”

“…The avascular lens contains an unusually high concentration of GSH which spontaneously, or as a cofactor of GPx and GST, reduces a variety of intracellular oxidizing species. Organic peroxides present in the circulation are, however, converted to correspondent alcohols, mainly by the plasma GPx-3 iso enzyme, a seleno-glycoprotein secreted to the blood by renal proximal tubules, but also expressed within the lens (12,13). Further solubilization of various epoxides, peroxides and lipid-derived aldehydes via GST-catalyzed conjugation with GSH enhances their removal from the blood.…”