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Human Red Blood Cell Uptake and Sequestration of Arsenite and Selenite: Evidence for the Formation of a Protective Glutathione Conjugate
Author(s) -
Leslie Elaine M.,
Kaur Gurnit,
Javed Warda,
Ponomarenko Olena,
Swanlund Diane P.,
Hu Michael,
Summers Kelly L.,
Casini Angela,
Wenzel Margot,
Casey Joseph R.,
Cordat Emmanuelle,
Pickering Ingrid J.,
George Graham N.
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.06204
Subject(s) - arsenite , selenium , arsenic , chemistry , glutathione , band 3 , red blood cell , carcinogen , biochemistry , dids , microbiology and biotechnology , biology , enzyme , membrane protein , organic chemistry , membrane
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) 2 AsSe] − , which undergoes biliary and fecal elimination. [(GS) 2 AsSe] − , 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 (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) 2 AsSe] − . 75 Se IV accumulation was inhibited by 4,4′‐diisothiocyanatodihydrostilbene‐2,2′‐disulfonic acid (H 2 DIDS) (IC 50 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 75 Se IV uptake. 73 As III uptake by human RBCs was temperature‐dependent and partly reduced by aquaglyceroporin 3 inhibitors. As III increased 75 Se IV accumulation (in the presence of albumin) and Se IV increased 73 As III accumulation in human RBCs. Near‐edge X‐ray absorption spectroscopy revealed the formation of [(GS) 2 AsSe] − in human RBCs exposed to both As III and Se IV . The sequestration of [(GS) 2 AsSe] − 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