A thiol-mediated active membrane transport of selenium by erythroid anion exchanger 1 protein

Abstract

In this paper, we describe a thiol-mediated and energy-dependent membrane transport of selenium by erythroid anion exchanger 1 (AE1, also known as band 3 protein). The AE1 is the most abundant integral protein of red cell membranes and plays a critical role in the carbon dioxide transport system in which carbon dioxide is carried as bicarbonate in the plasma. This protein mediates the membrane transport of selenium, an essential antioxidant micronutrient, from red cells to the plasma in a manner that is distinct from the already known anion exchange mechanism. In this pathway, selenium bound to the cysteine 93 of the hemoglobin β chain (Hb-Cysβ93) is transported by the relay mechanism to the Cys317 of the amino-terminal cytoplasmic domain of the AE1 on the basis of the intrinsic interaction between the two proteins and is subsequently exported to the plasma via the Cys843 of the membrane-spanning domain. The selenium export did not occur in plain isotonic buffer solutions and required thiols, such as albumin, in the outer medium. Such a membrane transport mechanism would also participate in the export pathways of the nitric oxide vasodilator activity and other thiol-reactive substances bound to the Hb-Cysβ93 from red cells to the plasma and/or peripherals. 2 IntroductionSelenium belongs to chalcogens that shares similar chemical properties especially with sulfur and, to a lesser extent, with tellurium. This element is an essential micronutrient for humans and other higher animal species. 1 Selenocysteine (SeCys), the 21st naturally occurring amino acid encoded by the UGA codon, is the form of selenium present in enzymes and proteins. In humans, 25 SeCys-containing proteins (selenoproteins) are identified on the basis of their selenoproteome analysis. 2 The best-known selenoproteins are the glutathione peroxidases (GPxs) that can catalyze the reduction of certain peroxide species (R−OOH) to the alcohols (R−OH) at their active center SeCys residue. 1,3 Nutritional selenium is thought to be obtained from a variety of selenium compounds in the diet, mostly in organic forms, such as SeCys and selenomethionine (SeMet). During the systemic delivery of selenium, selenoprotein P that is present in the plasma is thought to be the selenium supply protein for the biosynthesis of the other selenoproteins including GPxs. 4,5 Recent evidence in selenoprotein P (SelP) knockout mice has shown that the distribution of selenium from the liver to testis and brain is mediated by Sel P. 6,7 It is also found that in the absence of SelP, selenium from selenious acid (SA, H 2 SeO 3 ) in the diet can be distributed to the peripherals by a yet unknown mechanism. 8 So far, little is known about the membrane transport of selenium from selenium source compounds, including SA. Inorganic SA is rare as a chemical form of the food source compounds, but highly bioavailable SA is most frequently used as a source compound for the treatment of a selenium deficiency. 9Selenium-enriched yeast (a common form of selenium supplement) is found to contain ...

An effective method for profiling the selenium-binding proteins using its reactive metabolic intermediate

“…PenSSeSPen could possibly react with various biogenic thiols through the thiol exchange (Fig. 1b) [12,[22][23][24]. The elemental analysis results of PenSSeSPen used in this study were in good agreement with the calculated values.…”

“…We have demonstrated that this species allows reactions with certain endogenous protein thiols through thiol-exchange reactions and participating in the selenium transport (Fig. 1b) [12,[22][23][24]. A better understanding about the metabolism of selenium is also important from the viewpoints of both human health and toxicology, because the range of the selenium intake amount required for a trace nutrient is narrow when compared to some other nutrients [25].…”

Expansion of the APC superfamily of secondary carriers

“…It functions in chloride:bicarbonate exchange, selenium metabolism, volume regulation, erythrocyte cytoskeletal cell structure and metabolic coordination 45–47 . Its topology has been controversial, varying from 13 to 16 TMSs, depending on the prediction method used.…”

A Comprehensive Analysis of Selenium-Binding Proteins in the Brain Using Its Reactive Metabolite

“…When the PenSSeSPen sample was subjected to a MALDI TOF-MS analysis, the distinctive selenium isotopic pattern involving one selenium atom in a molecular ion was detected and the 80 Se-containing molecular ion peak was at m/z 376.3 (Calcd for 80 Se 376.2). PenSSeSPen can react with various biogenic thiols through the thiol-exchange reaction 27,33,34) ( Fig. 1).…”