Role of Selenoproteins in Redox Regulation of Signaling and the Antioxidant System: A Review

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.

A Mechanistic Link Between Selenium and Coronavirus Disease 2019 (COVID-19)

“…In the human body, selenium occurs mainly as a part of amino acid, selenocysteine, which is found in at least 25 selenocysteine-containing proteins called selenoproteins [4•, 53]. The major selenoproteins in human include five selenium-containing glutathione peroxidases (GPx1-4 and GPx6), three thioredoxin reductases (TrxR1-3), three iodothyronine deiodinases, one methionine sulfoxide reductase B1, selenoprotein P, H, K, M, N, R, S, and W, 15 kD selenoprotein, mitochondrial capsular selenoprotein and selenophosphate synthetase-2 [53][54][55].…”

A Surface Se‐Substituted LiCo[O2−δSeδ] Cathode with Ultrastable High‐Voltage Cycling in Pouch Full‐Cells

“…As we will discuss later in this work, during high‐voltage charging, the precoated Se would not only soak up the OL from the cathode to prevent it from attacking the electrolyte, but also substitute the oxidized O α − at the charged particle surface (Li 1− x Co+Se→Li 1− x Co[] +SeO 2 ) to eliminate oxygen vacancies and replenish electrons (Se→Se β + ) to the charged O α − ions (O α − →O 2− ), reducing the mobile O α − ions back to immobile O 2− at the charged particle surface, to shut down the global oxygen migration in the prolonged cycling. Se is a soft metalloid and an important antiaging element in biology [ 16 ] in the form of selenocysteine CH 2 SeH that captures the oxygen‐radical species in the human body. [ 17 ] In this study, we will show that Se would also have an “antiaging” effect on the high‐voltage LCO battery cycling by eliminating OL from the cathode.…”

Connection between the Altered HDL Antioxidant and Anti-Inflammatory Properties and the Risk to Develop Alzheimer’s Disease: A Narrative Review

“…GPx is the general term for a family of several selenium- (Se-) dependent isozymes that use reduced glutathione (GSH) as an obligate cosubstrate in the reduction of hydrogen peroxide to water [ 99 , 100 ]. Eight mammalian isoenzymes are known, with the intracellular and ubiquitous GPx-1 and GPx-4, the gastrointestinal GPx-4, and the plasma GPx-3 being the most abundant ones.…”

“…Eight mammalian isoenzymes are known, with the intracellular and ubiquitous GPx-1 and GPx-4, the gastrointestinal GPx-4, and the plasma GPx-3 being the most abundant ones. All members of the GPx family play, although to a different extent, a crucial role in the intracellular antioxidant defensive mechanism [ 100 ]. Indeed, besides the removal of mild reactive H 2 O 2 (mostly derived from the dismutation of superoxide produced in mitochondria), they can neutralize lipid hydroperoxides and halt the deleterious peroxidation of cell membranes [ 100 ].…”