Matsuoka T, Nishizaki T, Kisby G E
Department of Physiology, Kobe University School of Medicine, Japan.
J Neurochem. 1998 Feb;70(2):772-7. doi: 10.1046/j.1471-4159.1998.70020772.x.
Although cycasin (methylazoxymethanol beta-D-glucoside) is proposed to be a significant etiological factor for the prototypical neurodegenerative disorder Western Pacific amyotrophic lateral sclerosis and parkinsonism-dementia complex, the mechanism underlying transport of cycasin across the blood-brain barrier (BBB) is unknown. We examined cycasin transport in cultured bovine brain endothelial cells, a major element of the BBB. Cycasin was taken up into endothelial cells in a dose-dependent manner with maximal uptake observed at a concentration of 10 microM. Cycasin uptake was significantly inhibited by alpha-methyl-D-glucoside, a specific analogue for the Na+-dependent glucose transporter (SGLT), by the SGLT inhibitor phlorizin, by replacement of extracellular NaCl with LiCl, and by dinitrophenol (DNP), an inhibitor of energy metabolism. In addition, cycasin produced inward currents in a whole-cell voltage clamp configuration. Peak currents were observed at 10 microM with a trend toward reduction at higher concentrations, and currents were clearly blocked by alpha-methyl-D-glucoside, phlorizin, and DNP. In addition, cycasin never evoked currents in Na+-free extracellular solution. These results suggest that cycasin is selectively transported across brain endothelial cells, possibly across the BBB by a Na+/energy-dependent glucose transporter.
尽管苏铁素（甲基氧化偶氮甲醇β-D-葡萄糖苷）被认为是典型神经退行性疾病西太平洋肌萎缩侧索硬化症和帕金森病-痴呆综合征的一个重要病因，但苏铁素穿越血脑屏障（BBB）的潜在机制尚不清楚。我们研究了苏铁素在培养的牛脑内皮细胞（血脑屏障的主要组成部分）中的转运情况。苏铁素以剂量依赖的方式被内皮细胞摄取，在浓度为10微摩尔时观察到最大摄取量。α-甲基-D-葡萄糖苷（一种钠依赖性葡萄糖转运体（SGLT）的特异性类似物）、SGLT抑制剂根皮苷、用氯化锂替代细胞外氯化钠以及能量代谢抑制剂二硝基苯酚（DNP）均显著抑制了苏铁素的摄取。此外，苏铁素在全细胞电压钳模式下产生内向电流。在10微摩尔时观察到峰值电流，在更高浓度时有降低趋势，并且电流明显被α-甲基-D-葡萄糖苷、根皮苷和DNP阻断。此外，苏铁素在无钠的细胞外溶液中从未诱发电流。这些结果表明，苏铁素可选择性地穿越脑内皮细胞，可能通过钠/能量依赖性葡萄糖转运体穿越血脑屏障。
