Hemoglobin-mediated selenium export from red blood cells

Abstract

On the basis of the fact that selenium (Se) from selenite binds to hemoglobin (Hb), we investigated the missing process in the selenium export from red blood cells (RBCs), i.e., the transfer of selenium bound to Hb to RBC membrane proteins. To elucidate the molecular events of the Hbassociated selenium export from RBC, an Hb-Se complex was synthesized from thiol-exchange of Cys-β93 in Hb with penicillamine-substituted glutathione selenotrisulfide, as a model of major metabolic intermediates, and then interactions between the Hb-Se complex and RBC inside-out vesicles (IOVs) were examined. Selenium bound to Hb was transferred to the IOV membrane on the basis of the intrinsic interactions between Hb and the cytoplasmic domains of Band 3 protein (CDB3). The observed selenium transfer was inhibited by the pretreatments of IOVs with iodoacetamide and the α-chymotrypsin digestion, indicating that the Hb mediates the selenium transfer to the thiol groups of CDB3. In addition, it was found that deoxygenated Hb with a high binding affinity for CDB3 more favorably transferred selenium to the IOV membranes than oxygenated Hb with a low affinity. When selenium export from RBC to the plasma was examined by continuously introducing nitrogen gas, the selenium export rate was promoted with an increase in the rate of deoxygenated Hb. Overall, these data suggested that Hb could possibly play a role in the selenium export from RBC treated with selenite in an oxygen-linked fashion.

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

“…39 The vast majority of selenium (> 98 % of the total amount) in the SA-treated red cells is bound to Hb. 39 The selenium transport from Hb to the N-CPD of AE1 was thought to be the prerequisite event for the subsequent membrane transport of selenium to the plasma. Thus, the scaffold protein spectrins are unlikely to directly transport out selenium to the plasma.…”

“…40 Biogenic thiols in the bloodstream, such as Hb and glutathione in red cells and albumin in the plasma, can participate in the metabolism and/or transport of selenium species inside the red cells and the subsequent transport to the peripherals. 39,45,49 The thiols of spectrins can be interactive with glutathione to form disulfide bond, which associates to the flexible deformation of red cells in the peripheral capillaries. 50 Thus, spectrin thiols could possibly interact with selenium metabolites, and the selenium binding to spectrins was actually observed (Fig.…”

“…In our previous study using red cell inside-out vesicles, we demonstrated that selenium bound to Hb in the red cells is not transported to the N-CPD-deleted red cell membrane at all. 39 The vast majority of selenium (> 98 % of the total amount) in the SA-treated red cells is bound to Hb. 39 The selenium transport from Hb to the N-CPD of AE1 was thought to be the prerequisite event for the subsequent membrane transport of selenium to the plasma.…”

“…The selenium export to the plasma across the membranes occurs in an oxygen-linked fashion; it is enhanced by increasing the proportion of the deoxygenated Hb with a higher binding affinity for the N-CPD than the oxygenated Hb, similar to the NO export fashion. 39 Chemical modification of thiols in both the N-CPD and the MSD of the AE1 results in complete inhibition of the selenium export from red cells. 40 In the present study, we investigated the selenium transport mechanism across red cell membranes from Hb to the plasma and proposed a possible mechanism for a thiol-mediated membrane transport of selenium by the erythroid AE1 protein.…”

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

“…Selenotrisulfide (RSSeSR, STS), one of the reduced forms, was actually detected in a biological system, i.e., a selenium-enriched yeast sample using modern mass spectrometric techniques, 19) and its reactivity with biogenic protein thiols has been studied. [20][21][22][23][24] In our previous study, we investigated the reactivity of rat liver cytosolic proteins with STS as one of the reactive metabolic intermediates. 25) Several cytosolic proteins with Cys thiol were found to be reactive with a selenotrisulfide derivative through the thiol-exchange reaction.…”