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The MRP2/cMOAT Transporter and Arsenic-Glutathione Complex Formation Are Required for Biliary Excretion of Arsenic
Open accessAbstract
Worldwide, millions of people are exposed to arsenic in drinking water that exceeds the World Health Organization standard of 10 microg/liter by as much as 50-300-fold, yet little is known about the molecular basis for arsenic excretion. Here we show that transport of arsenic into bile depends on the MRP2/cMOAT transporter and that glutathione is obligatory for such transport. Using reversed phase liquid chromatography/mass spectrometry, we demonstrate that two arsenic-glutathione complexes not previously identified in vivo, arsenic triglutathione and methylarsenic diglutathione, account for most of the arsenic in the bile. The structure of the compounds was also confirmed by nuclear magnetic resonance spectroscopy. Our findings may help explain the increased susceptibility of malnourished human populations to arsenic.
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Cites
Griffith, O. W., & Meister, A. (1979) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)35980-5 · Cited by 1,683
Cited by
Deeley, R. G., Westlake, C., & Cole, S. P. C. (2006) · Physiological Reviews · doi:10.1152/physrev.00035.2005 · Cited by 761
Toxicological relevance of the multidrug resistance protein 1, MRP1 (ABCC1) and related transporters
Leslie, E. (2001) · Toxicology · doi:10.1016/s0300-483x(01)00454-1 · Cited by 376
Metabolism of arsenic and its toxicological relevance
Watanabe, T., & Hirano, S. (2013) · Archives of Toxicology · doi:10.1007/s00204-012-0904-5 · Cited by 324
ABC of oral bioavailability: transporters as gatekeepers in the gut
Dietrich, C. G., Geier, A., & Oude Elferink, R. P. J. (2003) · Gut · doi:10.1136/gut.52.12.1788 · Cited by 317
Metabolism, toxicity and anticancer activities of arsenic compounds
Khairul, I., Wang, Q. Q., Jiang, Y. H., Wang, C., & Naranmandura, H. (2017) · Oncotarget · doi:10.18632/oncotarget.14733 · Cited by 300
Metadata
- Authors
- Kala, S. V., Neely, M. W., Kala, G., Prater, C. I., Atwood, D. W., Rice, J. S., & Lieberman, M. W.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2000-10
- Volume
- 275
- Issue
- 43
- Pages
- 33404-33408
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1982330330
- Cited by
- 317
- References
- 1
- FWCI
- 13.14
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- The paper
- Kala, S. V., Neely, M. W., Kala, G., Prater, C. I., Atwood, D. W., Rice, J. S., & Lieberman, M. W. (2000). The MRP2/cMOAT Transporter and Arsenic-Glutathione Complex Formation Are Required for Biliary Excretion of Arsenic. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m007030200
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
