Metal transporters in intestine and brain: their involvement in metal-associated neurotoxicities
Metal transporters in intestine and brain: their involvement in metal-associated neurotoxicities
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DOI：
10.1177/0960327107070573
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发表时间：
2007-03-01
影响因子：
2.8
通讯作者：
Bannon, Desmond
中科院分区：
文献类型：
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作者：
Bressler, Joseph P.;Olivi, Luisa;Bannon, Desmond
必需金属和其他营养物质的运输通过严密的膜屏障，如胃肠道和血脑屏障是由特定的运输机制介导的。特定的转运体在细胞顶端表面吸收金属，并在基底外侧表面输出金属，并参与金属在细胞内的分布。每种主要必需金属钙、铁和锌的转运蛋白都已被确定。这些转运蛋白也介导非必需金属穿过紧密膜屏障的运输。例如，肠铁转运蛋白二价金属转运蛋白1介导铅和镉的摄取。必需金属的含量由转运者严格控制。当饮食中必需金属的水平较低时，肠道中相应的转运蛋白水平就会增加，此后有毒金属的运输就更有可能增加。在大脑中，对金属的严格调节可以防止由必需金属铁、铜和锌引起的氧化损伤。事实上，在神经退行性疾病中发现的氧化损伤很可能是由于这些金属的含量较高。在阿尔茨海默病的动物模型中，已经显示出细胞内铜和锌转运体的参与，这提高了铁、锌和铜水平升高可能是由于转运体活动中断所致的可能性。因此，暴露于影响转运蛋白活性的毒物可能导致神经退行性疾病的病因学/进展。
The transport of essential metals and other nutrients across tight membrane barriers such as the gastrointestinal tract and blood-brain barrier is mediated by specific transport mechanisms. Specific transporters take up metals at the apical surface and export them at the basolateral surface, and are involved in their intracellular distribution. Transporters for each of the major essential metals, calcium, iron and zinc, have been identified. These transporters also mediate the transport of non-essential metals across tight membrane barriers. For example, the intestinal iron transporter divalent metal transporter 1 mediates the uptake of lead and cadmium. The levels of essential metals are strictly regulated by transporters. When dietary levels of essential metals are low, levels of the corresponding transporters increase in the intestine, after which there is a greater potential for increased transport of toxic metals. In the brain, the strict regulation of metals prevents injury that potentially would result from oxidative damage induced by the essential metals iron, copper and zinc. Indeed, the oxidative damage found in neurodegenerative diseases is likely to be due to higher levels of these metals. Involvement of intracellular transporters for copper and zinc has been shown in animal models of Alzheimer's disease, raising the possibility that higher levels of iron, zinc and copper might be due to a disruption in the activity of transporters. Accordingly, exposure to toxicants that affect the activity of transporters potentially could contribute to the aetiology/progression of neurodegenerative diseases.