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

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• 作者：Elaine M. Leslie ; ^{eleslie@ualberta.ca}
• 关键词：Arsenic ; Glutathione ; ATP-binding cassette transporters ; MRP1/ABCC1 ; MRP2/ABCC2 ; Arsenic glutathione conjugates
• 刊名：Journal of Inorganic Biochemistry
• 出版年：2012
• 期刊代码：53_01620134
• 类别：ch
• 出版时间：March, 2012
• 卷：108
• 期：Complete
• 页码：141-149
• 文件大小：1058 K

摘要

Millions of people world-wide are chronically exposed to inorganic forms of the environmental toxicant arsenic in drinking water. This has led to a public health crisis because arsenic is a human carcinogen, and causes a myriad of other adverse health effects. In order to prevent and treat arsenic-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 (纬-Glu-Cys-Gly,GSH/GS) in the excretion of arsenic. The triglutathione conjugate of arsenite [As^III(GS)₃] and the diglutathione conjugate of monomethylarsonous acid [MMA^III(GS)₂] have been 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 (MRP1m>/ABCC1m>) and the related protein MRP2 (m>ABCC2m>), are thought to play an important role in arsenic detoxification through the cellular efflux of arsenic-GSH conjugates. Current knowledge on the cellular handling of arsenic with a special emphasis on the transport pathways of the arsenic-GSH conjugates As^III(GS)₃, MMA^III(GS)₂, and dimethylarsenic glutathione DMA^III(GS), as well as, the seleno-bis(m>Sm>-glutathionyl) arsinium ion [(GS)₂AsSe]^{鈭?/sup> are reviewed.}