Arsenic-glutathione conjugate transport by the human multidrug resistance proteins (MRPs/ABCCs)

Millions of people world-wide are chronically exposed to inorganic forms of the environmental toxicant arsenic (As) in drinking water. This has led to a public health crisis because As is a human carcinogen, and causes a myriad of other adverse health effects. In order to prevent and treat As-induced toxicity it is critical to understand the cellular handling of this metalloid. A large body of literature describes the importance of the cellular tripeptide glutathione (ç-Glu-Cys-Gly,GSH/GS) in the excretion of As. The triglutathione conjugate of arsenite [fusion_builder_container hundred_percent=”yes” overflow=”visible”][fusion_builder_row][fusion_builder_column type=”1_1″ background_position=”left top” background_color=”” border_size=”” border_color=”” border_style=”solid” spacing=”yes” background_image=”” background_repeat=”no-repeat” padding=”” margin_top=”0px” margin_bottom=”0px” class=”” id=”” animation_type=”” animation_speed=”0.3″ animation_direction=”left” hide_on_mobile=”no” center_content=”no” min_height=”none”][AsIII(GS)3] and the diglutathione conjugate of monomethylarsonous acid [MMAIII(GS)2] were isolated from rat bile and mouse urine, and account for the majority of excreted arsenic, suggesting these are important transportable forms. The ATP-binding cassette (ABC) transporter proteins, multidrug resistance protein 1 (MRP1/ABCC1) and the related protein MRP2 (ABCC2), are thought to play an important role in As detoxification through the cellular efflux of As-GSH conjugates. Current knowledge on the cellular handling of As with a special emphasis on the transport pathways of the As-GSH conjugates AsIII(GS)3, MMAIII(GS)2, and dimethylarsenic glutathione DMAIII(GS), as well as, the seleno-bis(S-glutathionyl) arsinium ion [(GS)2AsSe]- are reviewed.

Author: Leslie, Elaine M. ;Full Source: Journal of Inorganic Biochemistry [online computer file] 2012, 108(1), 141-149 (Eng) ;