TY - JOUR
T1 - Trivalent arsenicals and glucose use different translocation pathways in mammalian GLUT1
AU - Jiang, Xuan
AU - McDermott, Joseph R.
AU - Abdul Ajees, A.
AU - Rosena, Barry P.
AU - Liu, Zijuan
PY - 2010
Y1 - 2010
N2 - 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 CH 3As(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.
AB - 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 CH 3As(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.
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U2 - 10.1039/b920471g
DO - 10.1039/b920471g
M3 - Article
C2 - 21069159
AN - SCOPUS:77953657278
SN - 1756-5901
VL - 2
SP - 211
EP - 219
JO - Metallomics
JF - Metallomics
IS - 3
ER -