Trivalent arsenicals and glucose use different translocation pathways in mammalian GLUT1

Xuan Jiang, Joseph R. McDermott, A. Abdul Ajees, Barry P. Rosena, Zijuan Liu

Research output: Contribution to journalArticlepeer-review

37 Citations (Scopus)

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 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.

Original languageEnglish
Pages (from-to)211-219
Number of pages9
JournalMetallomics
Volume2
Issue number3
DOIs
Publication statusPublished - 19-03-2010

All Science Journal Classification (ASJC) codes

  • Chemistry (miscellaneous)
  • Biophysics
  • Biochemistry
  • Biomaterials
  • Metals and Alloys

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