Scott Jordan, Opejin Adeleye, Tidball Andrew, Stehouwer Nathan, Rekman Janelle, Louters Larry L
Department of Chemistry and Biochemistry, Calvin College, Grand Rapids, MI 49546, USA.
Chem Biol Interact. 2009 Dec 10;182(2-3):199-203. doi: 10.1016/j.cbi.2009.08.008. Epub 2009 Aug 15.
An early event in the toxic effects of organic arsenic compounds, such as phenylarsine oxide (PAO), is an inhibition of glucose uptake. Glucose uptake involving the glucose transporter, GLUT4 is inhibited by PAO indicating an importance of vicinal sulfhydryls in insulin-stimulated glucose uptake. However, the data on effects of PAO on GLUT1 are conflicting. This study investigated the effects of PAO on glucose uptake in L929 fibroblast cells, cells, which express only GLUT1. The data presented here reveal a dual effect of PAO. At low concentrations or short exposure times PAO stimulated glucose uptake reaching a peak activation of about 400% at 3 microM. At higher concentrations (40 microM), PAO clearly inhibited glucose uptake. At intermediate concentrations (10 microM), PAO had no effect under basal conditions but completely inhibited activation of glucose uptake by glucose deprivation and partially inhibited methylene blue-stimulated glucose uptake. PAO increased the specific binding of cytochalasin B to GLUT1 suggesting a direct interaction with the transporter. These data are most consistent with PAO interacting with multiple proteins that regulate the activity of this transporter, one of which may be GLUT1 itself. The identity of these proteins will require further investigation.
有机砷化合物（如苯胂化氧，PAO）毒性作用的早期事件之一是抑制葡萄糖摄取。涉及葡萄糖转运蛋白GLUT4的葡萄糖摄取受到PAO抑制，这表明相邻巯基在胰岛素刺激的葡萄糖摄取中具有重要作用。然而，关于PAO对GLUT1影响的数据存在矛盾。本研究调查了PAO对仅表达GLUT1的L929成纤维细胞葡萄糖摄取的影响。此处呈现的数据揭示了PAO的双重作用。在低浓度或短暴露时间下，PAO刺激葡萄糖摄取，在3 microM时达到约400%的峰值激活。在较高浓度（40 microM）下，PAO明显抑制葡萄糖摄取。在中等浓度（10 microM）下，PAO在基础条件下无作用，但完全抑制葡萄糖剥夺引起的葡萄糖摄取激活，并部分抑制亚甲蓝刺激的葡萄糖摄取。PAO增加了细胞松弛素B与GLUT1的特异性结合，表明其与转运蛋白存在直接相互作用。这些数据最符合PAO与多种调节该转运蛋白活性的蛋白质相互作用的情况，其中之一可能是GLUT1本身。这些蛋白质的身份有待进一步研究。
