期刊
JOURNAL OF INORGANIC BIOCHEMISTRY
卷 108, 期 -, 页码 141-149出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jinorgbio.2011.11.009
关键词
Arsenic; Glutathione; ATP-binding cassette transporters; MRP1/ABCC1; MRP2/ABCC2; Arsenic glutathione conjugates
资金
- Canadian Institutes of Health Research (CIHR) [MOP-84218]
- Alberta Cancer Foundation
- Alberta Innovates Health Solutions (AIHS)
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 (gamma-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 (MRP1/ABCC1) and the related protein MRP2 (ABCC2), 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(S-glutathionyl) arsinium ion [(GS)(2)AsSe](-) are reviewed. (c) 2011 Elsevier Inc. All rights reserved.
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