| Methylarsonous Acid Transport by Aquaglyceroporins Zijuan Liu,1 Miroslav Styblo,2 and Barry P. Rosen1 1Department of Biochemistry and Molecular Biology, Wayne State University, School of Medicine, Detroit, Michigan, USA; 2Department of Nutrition, School of Public Health, and the Center for Environmental Medicine, Asthma, and Lung Biology, School of Medicine, University of North Carolina-Chapel Hill, Chapel Hill, North Carolina, USA Abstract
Many mammals methylate trivalent inorganic arsenic in liver to species that are released into the bloodstream and excreted in urine and feces. This study addresses how methylated arsenicals pass through cell membranes. We have previously shown that aquaglyceroporin channels, including Escherichia coli GlpF, Saccharomyces cerevisiae Fps1p, AQP7, and AQP9 from rat and human, conduct trivalent inorganic arsenic [As(III) ] as arsenic trioxide, the protonated form of arsenite. One of the initial products of As(III) methylation is methylarsonous acid [MAs(III) ], which is considerably more toxic than inorganic As(III) . In this study, we investigated the ability of GlpF, Fps1p, and AQP9 to facilitate movement of MAs(III) and found that rat aquaglyceroporin conducted MAs(III) at a higher rate than the yeast homologue. In addition, rat AQP9 facilitates MAs(III) at a higher rate than As(III) . These results demonstrate that aquaglyceroporins differ both in selectivity for and in transport rates of trivalent arsenicals. In this study, the requirement of AQP9 residues Phe-64 and Arg-219 for MAs(III) movement was examined. A hydrophobic residue at position 64 is not required for MAs(III) transport, whereas an arginine at residue 219 may be required. This is similar to that found for As(III) , suggesting that As(III) and MAs(III) use the same translocation pathway in AQP9. Identification of MAs(III) as an AQP9 substrate is an important step in understanding physiologic responses to arsenic in mammals, including humans. Key words: arsenic trioxide, AQP9, aquaglyceroporin, methylarsonous acid. Environ Health Perspect 114:527-531 (2006) . doi:10.1289/ehp.8600 available via http://dx.doi.org/ [Online 2 December 2005]
Address correspondence to B.P. Rosen, Department of Biochemistry and Molecular Biology, Wayne State University, School of Medicine, 540 E. Canfield Ave., Detroit, MI 48201 USA. Telephone: (313) 577-1512. Fax: (313) 577-2765. E-mail: brosen@med.wayne.edu We thank W.R. Cullen for the generous gift of MAs(III) . This work was supported by National Institute of Health (NIH) grants ES10344 and GM55425 and a pilot project grant from the Wayne State University Environmental Health Sciences Center in Molecular and Cellular Toxicology with Human Applications (B.P.R.) ; American Heart Association postdoctoral fellowship 0520014Z (Z.L.) ; and NIH grant ES09941, U.S. Environmental Protection Agency cooperative agreement CR829522, and Clinical Nutrition Research Center grant DK 56350 (M.S.) . The authors declare they have no competing financial interests. Received 20 August 2005 ; accepted 1 December 2005.
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