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

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

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 et al. Biochem Pharmacol. 2020 Oct.

. 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.

PubMed Disclaimer

Publication types

Actions
Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Substances

Actions
Actions
Actions
Actions

Grants and funding

P41 GM103393/GM/NIGMS NIH HHS/United States

LinkOut - more resources

Full Text Sources
- Elsevier Science
- Ovid Technologies, Inc.
Research Materials
- NCI CPTC Antibody Characterization Program
Miscellaneous
- NCI CPTAC Assay Portal

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

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

Affiliations

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

Authors

Affiliations

Abstract

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Research Materials

Miscellaneous