Manganese distribution across the blood-brain barrier III - The divalent metal transporter-1 is not the major mechanism mediating brain manganese uptake
Manganese distribution across the blood-brain barrier III - The divalent metal transporter-1 is not the major mechanism mediating brain manganese uptake
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DOI：
10.1016/j.neuro.2003.10.005
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发表时间：
2004-03-01
期刊：
影响因子：
3.4
通讯作者：
Yokel, RA
中科院分区：
文献类型：
--
作者：
Crossgrove, JS;Yokel, RA
锰（Mn）对大脑是必需的，也是有毒的。脑Mn摄取利用扩散和转运蛋白介导的途径。二价金属转运蛋白-1（DMT-1）已被认为介导脑锰摄取。B/B Belgrade大鼠不表达显著量的功能性DMT-1。本工作采用原位脑灌注技术测定了B/B和+/B Belgrade和Wistar大鼠的Mn-54离子和Mn-54转铁蛋白（Mn Tf）的脑内流传递系数。脑锰摄取量没有显着差异的三种大鼠品系的锰物种。我们假设Mn可能通过DMT-1非依赖性过程进入脑内皮细胞，但由于缺乏DMT-1活性而不能分布在这些细胞中进入脑组织。为了检验这一假设，在原位脑灌注后从B/B和+/B Belgrade大鼠和Wistar大鼠分离脑毛细血管内皮细胞。一些动物在原位脑灌注后接受脑血管冲洗，以确定基因型对Mn-54吸附到内皮细胞腔表面的任何影响。Mn-54离子或Mn-54 Tf灌注后，不到30%的脑Mn-54仍与内皮细胞结合，表明大部分已分布到脑细胞外液（ECF）和/或脑细胞中。Mn似乎通过除DMT-1以外的一种或多种载体介导的过程穿过大鼠血脑屏障（BBB）分布到脑中。(C)2003年爱思唯尔公司All rights reserved.
Manganese (Mn) is essential for and toxic to the brain. Brain Mn uptake utilizes both diffusion and transporter-mediated pathways. The divalent metal transporter-1 (DMT-1) has been suggested to mediate brain Mn uptake. The b/b Belgrade rat does not express significant amounts of functional DMT-1. In the present work, brain influx transfer coefficients of Mn-54 ion and Mn-54 transferrin (Mn Tf) were determined in b/b and +/b Belgrade and Wistar rats using the in situ brain perfusion technique. Brain Mn uptake was not significantly different among the three rat strains for either Mn species. We hypothesized that Mn may enter brain endothelial cells by a DMT-1-independent process but not be able to distribute across those cells into brain tissue due to the absence of DMT-1 activity. To test this hypothesis the brain capillary endothelial cells were isolated from b/b and +/b Belgrade rats and Wistar rats after in situ brain perfusion. Some animals received cerebrovascular washout after in situ brain perfusion to ascertain any affect of genotype on Mn-54 adsorption to the endothelial cell luminal surface. Less than 30% of the brain Mn-54 after Mn-54 ion or Mn-54 Tf perfusion remained associated with endothelial cells, suggesting the majority had distributed into brain extracellur fluid (ECF) and/or brain cells. Mn appears to distribute across the rat blood-brain barrier (BBB) into the brain by one or more carrier-mediated processes other than the DMT-1. (C) 2003 Elsevier Inc. All rights reserved.