Human red blood cell uptake and sequestration of arsenite and selenite: Evidence of seleno-bis(S-glutathionyl) arsinium ion formation in human cells

Gurnit Kaur; Warda Javed; Olena Ponomarenko; Kamran Shekh; Diane P Swanlund; Janet R Zhou; Kelly L Summers; Angela Casini; Margot N Wenzel; Joseph R Casey; Emmanuelle Cordat; Ingrid J Pickering; Graham N George; Elaine M Leslie

doi:10.1016/j.bcp.2020.114141

Human red blood cell uptake and sequestration of arsenite and selenite: Evidence of seleno-bis(S-glutathionyl) arsinium ion formation in human cells

Biochem Pharmacol. 2020 Oct:180:114141. doi: 10.1016/j.bcp.2020.114141. Epub 2020 Jul 8.

Authors

Affiliations

¹ Division of Analytical and Environmental Toxicology, Department of Laboratory Medicine and Pathology, University of Alberta, Canada; Membrane Protein Disease Research Group, University of Alberta, Canada.
² Membrane Protein Disease Research Group, University of Alberta, Canada; Department of Physiology, University of Alberta, Canada.
³ Department of Geological Sciences, University of Saskatchewan, Canada.
⁴ Department of Geological Sciences, University of Saskatchewan, Canada; Department of Chemistry, University of Saskatchewan, Canada.
⁵ School of Chemistry, Cardiff University, UK; Department of Chemistry, Technical University of Munich, Germany.
⁶ School of Chemistry, Cardiff University, UK.
⁷ Membrane Protein Disease Research Group, University of Alberta, Canada; Department of Physiology, University of Alberta, Canada; Department of Biochemistry, University of Alberta, Canada.
⁸ Division of Analytical and Environmental Toxicology, Department of Laboratory Medicine and Pathology, University of Alberta, Canada; Membrane Protein Disease Research Group, University of Alberta, Canada; Department of Physiology, University of Alberta, Canada. Electronic address: eleslie@ualberta.ca.

PMID: 32652143
DOI: 10.1016/j.bcp.2020.114141

Abstract

Over 200 million people worldwide are exposed to the 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 slows the distribution of both compounds to peripheral tissues susceptible to toxic effects. In human RBCs, the influence of arsenic on selenium accumulation, and vice versa, is largely unknown. The study aims were to characterize arsenite (As^III) and selenite (Se^IV) uptake by human RBCs, to determine if Se^IV and As^III 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]^-. ⁷⁵Se^IV accumulation was temperature and Cl^--dependent, inhibited by 4,4'-diisothiocyanatodihydrostilbene-2,2'-disulfonic acid (H₂DIDS) (IC₅₀ 1 ± 0.2 µM), and approached saturation at 30 µM, suggesting uptake is mediated by the erythrocyte anion-exchanger 1 (AE1 or Band 3, gene SLC4A1). HEK293 cells overexpressing AE1 showed concentration-dependent ⁷⁵Se^IV uptake. ⁷³As^III uptake by human RBCs was temperature-dependent, partly reduced by aquaglyceroporin 3 inhibitors, and not saturated. As^III increased ⁷⁵Se^IV accumulation (in the presence of albumin) and Se^IV increased ⁷³As^III accumulation in human RBCs. Near-edge X-ray absorption spectroscopy revealed the formation of [(GS)₂AsSe]^- in human RBCs exposed to both As^III and Se^IV. The sequestration of [(GS)₂AsSe]^- in human RBCs potentially slows arsenic distribution to susceptible tissues and could reduce arsenic-induced disease.

Keywords: Anion exchanger 1 (SLC4A1); Arsenic; Human red blood cells; Selenium; Seleno-bis(S-glutathionyl) arsinium.

Publication types

Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Arsenites / blood*
Arsenites / pharmacology
Biological Transport / drug effects
Biological Transport / physiology
Dose-Response Relationship, Drug
Erythrocytes / drug effects
Erythrocytes / metabolism*
Glutathione / blood*
HEK293 Cells
Humans
Selenious Acid / blood*
Selenious Acid / pharmacology
X-Ray Absorption Spectroscopy / methods

Substances

Arsenites
Selenious Acid
Glutathione
arsenite

Grants and funding

P41 GM103393/GM/NIGMS NIH HHS/United States