title: Mammalian glucose permease GLUT1 facilitates transport of arsenic trioxide and methylarsonous acid.
abstract: Arsenic exposure is associated with hypertension, diabetes, and cancer. Some mammals methylate arsenic. Saccharomyces cerevisiae hexose permeases catalyze As(OH)(3) uptake. Here, we report that mammalian glucose transporter GLUT1 catalyzes As(OH)(3) and CH(3)As(OH)(2) uptake in yeast or in Xenopus laevis oocytes. Expression of GLUT1 in a yeast lacking other glucose transporters allows for growth on glucose. Yeast expressing yeast HXT1 or rat GLUT1 transport As(OH)(3) and CH(3)As(OH)(2). The K(m) of GLUT1 is to 1.2mM for CH(3)As(OH)(2), compared to a K(m) of 3mM for glucose. Inhibition between glucose and CH(3)As(OH)(2) is noncompetitive, suggesting differences between the translocation pathways of hexoses and arsenicals. Both human and rat GLUT1 catalyze uptake of both As(OH)(3) and CH(3)As(OH)(2) in oocytes. Thus GLUT1 may be a major pathway uptake of both inorganic and methylated arsenicals in erythrocytes or the epithelial cells of the blood-brain barrier, contributing to arsenic-related cardiovascular problems and neurotoxicity.
authors.affiliation: Department of Biochemistry and Molecular Biology, Wayne State University, School of Medicine, Detroit, MI 48201, USA.
authors.forename: Zijuan
authors.initials: Z
authors.lastname: Liu
authors.forename: Marco A
authors.initials: MA
authors.lastname: Sanchez
authors.forename: Xuan
authors.initials: X
authors.lastname: Jiang
authors.forename: Eckhard
authors.initials: E
authors.lastname: Boles
authors.forename: Scott M
authors.initials: SM
authors.lastname: Landfear
authors.forename: Barry P
authors.initials: BP
authors.lastname: Rosen
mesh_terms: D000818:Animals; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000378:metabolism*; D001693:Biological Transport, Active; D003001:Cloning, Molecular; D005576:Colforsin / Q000494:pharmacology; D003571:Cytochalasin B / Q000494:pharmacology; D005260:Female; D051246:Glucose Transport Proteins, Facilitative; D051272:Glucose Transporter Type 1 / Q000502:physiology*; D006601:Hexoses / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D009004:Monosaccharide Transport Proteins / Q000378:metabolism*; D009865:Oocytes / Q000378:metabolism; D010087:Oxides / Q000378:metabolism*; D051381:Rats; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D014982:Xenopus laevis
chemical_list: D001152:Arsenicals; D051246:Glucose Transport Proteins, Facilitative; D051272:Glucose Transporter Type 1; C090594:HXT1 protein, S cerevisiae; D006601:Hexoses; D009004:Monosaccharide Transport Proteins; D010087:Oxides; C495677:SLC2A1 protein, human; D029701:Saccharomyces cerevisiae Proteins; C495679:Slc2a1 protein, rat; D005576:Colforsin; D003571:Cytochalasin B; C020300:monomethylarsonic acid; D000077237:Arsenic Trioxide