Abstract
Selenium is a vital trace element present as selenocysteine (Sec) in proteins that are, thus, known as selenoproteins. Humans have 25 selenoproteins, most of which are functionally characterized as oxidoreductases, where the Sec residue plays a catalytic role in redox regulation and antioxidant activity. Glutathione peroxidase plays a pivotal role in scavenging and inactivating hydrogen and lipid peroxides, whereas thioredoxin reductase reduces oxidized thioredoxins as well as non-disulfide substrates, such as lipid hydroperoxides and hydrogen peroxide. Selenoprotein R protects the cell against oxidative damage by reducing methionine-R-sulfoxide back to methionine. Selenoprotein O regulates redox homeostasis with catalytic activity of protein AMPylation. Moreover, endoplasmic reticulum (ER) membrane selenoproteins (SelI, K, N, S, and Sel15) are involved in ER membrane stress regulation. Selenoproteins containing the CXXU motif (SelH, M, T, V, and W) are putative oxidoreductases that participate in various cellular processes depending on redox regulation. Herein, we review the recent studies on the role of selenoproteins in redox regulation and their physiological functions in humans, as well as their role in various diseases.
Highlights
Most reactive oxygen species (ROS) are generated as by-products of cellular redox processes, including mitochondrial respiration and are known to be harmful to human health when their cellular levels exceed the physiologically acceptable level
We provide a brief overview of the various functions of selenoproteins and their roles in redox regulation and physiological functions
Organisms contain an array of defense systems, such as the thiol-dependent antioxidant system, which coordinate to remove ROS and reactive nitrogen species
Summary
Most reactive oxygen species (ROS) are generated as by-products of cellular redox processes, including mitochondrial respiration and are known to be harmful to human health when their cellular levels exceed the physiologically acceptable level. Antioxidants 2020, 9, 383 disorders, ischemia/reperfusion injury, age-related alterations, dysfunctions related to immune defense and inflammatory responses, and other diseases [1,2,3,4,5,6,7,8,9,10,11] Antioxidant enzymes such as superoxide dismutase, catalase, and other redox enzymes, including selenoproteins, and low weight antioxidant molecules such as carotenoids, ascorbate, vitamin E, α-lipoic acid, and glutathione (GSH) are essential for maintaining the “steady state” concentration of ROS, which helps to regulate the redox balance and maintain cellular homeostasis. Most functionally characterized selenoproteins have catalytic activities owing to their selenocysteine (Sec) residue and act to neutralize and remove ROS We provide a brief overview of the various functions of selenoproteins and their roles in redox regulation and physiological functions
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