Arsenic and Selenium Efflux from Human Red Blood Cells

Abstract ID 90721 Poster Board 410 Chronic exposure to arsenic (As), a human carcinogen is a massive global health concern affecting millions of people across the world; it can cause lung, skin, and bladder cancers and is associated with kidney and liver tumours, cardiovascular disease, and diabetes. Consumption of groundwater naturally contaminated with inorganic As is the major exposure source. In many regions, removal is economically unfeasible, so toxicity prevention and treatment strategies are greatly needed. A surprising mutually protective relationship was discovered between As and the essential trace element selenium (Se); reduced glutathione (γ-Glu-Cys-Gly), As and Se form a complex, the seleno-bis (S-glutathionyl) arsinium ion ([(GS)₂AsSe]⁻), in red blood cells (RBCs), where [(GS)₂AsSe]⁻ is then retained. This sequestration of both compounds is protective because it slows their distribution to other tissues in the body. [(GS)₂AsSe]⁻ does not undergo ATP-dependent transport across human erythrocyte membrane vesicles, but As and Se leave rodent RBCs within 24 hours, leading us to hypothesize that [(GS)₂AsSe]⁻ dissociates into As and Se prior to exit from the human RBCs. The objectives of this study were to characterize the influence of As and Se on each other's export from human RBCs, and to identify the mechanisms of As and Se efflux from human RBCs. We propose that As will be exported as As(OH)₃ by aquaglyceroporin 3 (AQP3) and/or as As(GS)₃ by the ATP-binding cassette transporter multidrug resistance protein 1 (MRP1/ABCC1), and that Se will be exported as HSe⁻ by the anion exchanger 1 (AE1/SLC4A1). Transport assays with human RBCs were performed using radioactive forms of As and Se (50 nCi, 1 μM), and export of Se was reduced by the presence of As by 1.8- to 2.6-fold at 0 to 360 minutes. Transport of As was reduced by the presence of Se by 1.5- to 4.1- fold at 0 to 360 minutes. After 24 hours, export of As in the presence and absence of Se (and vice versa) was not significantly different, indicating that As and Se contribute to retention of each in human RBCs but As and Se are eventually exported. The pharmacological inhibitors of AQP3 (Auphen) and AE1 (DIDS) inhibited uptake of As and Se, respectively, but did not have statistically significant effects on As or Se efflux from human RBCs. These data suggest AQP3 and AE1 are not involved in As and Se export from human RBCs, but both efflux pathway need further characterization. Understanding how As and Se leave the human RBCs is important for understanding their toxicity and ultimately preventing it. This research was funded by the Canadian Institutes of Health Research (grant number PJT-159547).