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- W3016794893 abstract "Over 200 million people worldwide are exposed to the proven human carcinogen, arsenic, in contaminated drinking water. In laboratory animals, arsenic and the essential trace element, selenium, can undergo mutual detoxification through the formation of the seleno-bis(S-glutathionyl) arsinium ion [(GS)2AsSe]−, which undergoes biliary and fecal elimination. [(GS)2AsSe]−, formed in animal red blood cells (RBCs), sequesters arsenic and selenium, and likely slows the distribution of both metalloids to the liver, and other organs susceptible to toxic effects. In human RBCs, the influence of arsenic on selenium accumulation, and vice versa, is largely unknown. The aims of this study were to characterize arsenite (AsIII) and selenite (SeIV) uptake by human RBCs, to determine if SeIV and AsIII increase the respective accumulation of the other in human RBCs, and ultimately to determine if this occurs through the formation and sequestration of [(GS)2AsSe]−. 75SeIV accumulation was inhibited by 4,4′-diisothiocyanatodihydrostilbene-2,2′-disulfonic acid (H2DIDS) (IC50 1 ± 0.2 μM), suggesting uptake is mediated by the erythrocyte anion-exchanger 1 (AE1 or Band 3, gene SLC4A1). HEK293 cells overexpressing AE1 showed concentration-dependent 75SeIV uptake. 73AsIII uptake by human RBCs was temperature-dependent and partly reduced by aquaglyceroporin 3 inhibitors. AsIII increased 75SeIV accumulation (in the presence of albumin) and SeIV increased 73AsIII accumulation in human RBCs. Near-edge X-ray absorption spectroscopy revealed the formation of [(GS)2AsSe]− in human RBCs exposed to both AsIII and SeIV. The sequestration of [(GS)2AsSe]− in human RBCs potentially slows arsenic distribution to susceptible tissues and could reduce arsenic-induced disease. Support or Funding Information Canadian Institutes of Health Research, Canada Research Chairs program, Natural Science and Engineering Council of Canada" @default.
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- W3016794893 date "2020-04-01" @default.
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- W3016794893 title "Human Red Blood Cell Uptake and Sequestration of Arsenite and Selenite: Evidence for the Formation of a Protective Glutathione Conjugate" @default.
- W3016794893 doi "https://doi.org/10.1096/fasebj.2020.34.s1.06204" @default.
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