Methylarsonous Acid Transport by Aquaglyceroporins

摘要

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 Fpslp,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.