Department of Biochemistry, Wayne State University, School of Medicine, Detroit, Michigan, USA.
Metallomics. 2010 Mar;2(3):211-9. doi: 10.1039/b920471g. Epub 2009 Dec 8.
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 Ser(66), Arg(126) and Thr(310), residues critical for glucose uptake, led to decreased uptake of glucose but increased uptake of CH₃As(OH)₂. The K(m) 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 (P(f)) 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.
大鼠葡萄糖转运蛋白同工型 1 或 rGLUT1 在新生儿心脏和形成血脑屏障的上皮细胞中表达，促进三价砷化合物亚砷酸盐（As(OH)₃）和甲基砷酸盐（CH₃As(OH)₂）的摄取。GLUT1 可能是砷进入心脏和大脑的主要途径，在那里类金属会引起心脏毒性和神经毒性。在本文中，我们比较了 GLUT1 对三价甲基砷酸盐和葡萄糖的转运特性。取代 Ser(66)、Arg(126)和 Thr(310)，这些残基对葡萄糖摄取至关重要，导致葡萄糖摄取减少，但 CH₃As(OH)₂摄取增加。三个鉴定突变体 S66F、R126K 和 T310I 的 CH₃As(OH)₂摄取 K(m) 值比天然 GLUT1 降低了 4-10 倍。GLUT1 和三个临床分离株的渗透水通透性系数 (P(f)) 与 CH₃As(OH)₂摄取率平行增加。GLUT1 抑制剂 Hg(II)、细胞松弛素 B 和 forskolin 减少了葡萄糖的摄取，但不减少 CH₃As(OH)₂的摄取。这些结果表明，CH₃As(OH)₂和水在 GLUT1 中使用共同的转运途径，与葡萄糖转运途径不同。
