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Issue 3, 2010
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Trivalent arsenicals and glucose use different translocation pathways in mammalian GLUT1

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Abstract

Rat glucose transporter isoform 1 or rGLUT1, which is expressed in neonatal heart and the epithelial cells that form the blood–brain barrier, facilitates uptake of the trivalent arsenicals arsenite as As(OH)3 and methylarsenite as CH3As(OH)2. GLUT1 may be the major pathway for arsenic uptake into heart and brain, where the metalloid causes cardiotoxicity and neurotoxicity. In this paper, we compare the translocation properties of GLUT1 for trivalent methylarsenite and glucose. Substitution of Ser66, Arg126 and Thr310, residues critical for glucose uptake, led to decreased uptake of glucose but increased uptake of CH3As(OH)2. The Km for uptake of CH3As(OH)2 of three identified mutants, S66F, R126K and T310I, were decreased 4–10 fold compared to native GLUT1. The osmotic water permeability coefficient (Pf) of GLUT1 and the three clinical isolates increased in parallel with the rate of CH3As(OH)2 uptake. GLUT1 inhibitors Hg(II), cytochalasin B and forskolin reduced uptake of glucose but not CH3As(OH)2. These results indicate that CH3As(OH)2 and water use a common translocation pathway in GLUT1 that is different to that of glucose transport.

Graphical abstract: Trivalent arsenicals and glucose use different translocation pathways in mammalian GLUT1

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Publication details

The article was received on 01 Oct 2009, accepted on 24 Nov 2009, published on 08 Dec 2009 and first published online on 08 Dec 2009


Article type: Paper
DOI: 10.1039/B920471G
Citation: Metallomics, 2010,2, 211-219
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    Trivalent arsenicals and glucose use different translocation pathways in mammalian GLUT1

    X. Jiang, J. R. McDermott, A. A. Ajees, B. P. Rosen and Z. Liu, Metallomics, 2010, 2, 211
    DOI: 10.1039/B920471G

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