Synergism in aluminum and mercury neurotoxicity.
Synergism in aluminum and mercury neurotoxicity.
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DOI：
10.15761/ifnm.1000214
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发表时间：
2018-05
期刊：
影响因子：
--
通讯作者：
Lukiw WJ
中科院分区：
文献类型：
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作者：
Alexandrov PN;Pogue AI;Lukiw WJ
铝和汞是我们环境中常见的神经毒性污染物-从我们呼吸的空气到我们饮用的水再到我们吃的食物。值得注意的是，迄今为止，这两种公认的环境神经毒素（即对脑细胞具有一般毒性的毒素）和遗传毒素（对遗传器官具有直接毒性的物质）均未进行过严格研究，也未在人类神经生物学或人类中枢神经系统（CNS）细胞中评价过其神经毒性。在本文中，我们报告了添加铝[硫酸铝（SO ↓ [2]）↓ [2]]和/或汞[硫酸盐; HgSO ↓ [4]]的影响，以人类神经胶质细胞（HNG）细胞在原代共培养使用的促炎性转录因子NF-κ B（p50/p65）复合物的演变作为一个关键指标的发病炎症神经变性和致病性炎症信号。如通过NF-kB（p50/p65）复合物的显著诱导所指示的，结果表明：（i）在环境20-200 nM范围内，由这两种环境神经毒素中的每一种向HNG细胞传递的促炎信号传导显著增加;和（ii）当铝（硫酸盐）和汞（硫酸盐）一起添加时，神经毒性显著协同。这是第一份关于硫酸铝和/或硫酸汞对原代培养人脑细胞炎症信号启动的神经毒性作用的报告。铝+汞共同对其他神经学上重要的信号分子的影响，或常见环境金属神经毒素的其他组合对人类神经生物学的影响，目前仍不清楚，但肯定需要在实验室动物、人类中枢神经系统细胞的原代组织培养物和其他神经生物学上现实的实验测试系统中进行额外的调查和进一步研究。
Aluminum and mercury are common neurotoxic contaminants in our environment – from the air we breathe to the water that we drink to the foods that we eat. It is remarkable that to date neither of these two well-established environmental neurotoxins (i.e. those having a general toxicity towards brain cells) and genotoxins (those agents which exhibit directed toxicity toward the genetic apparatus) have been critically studied, nor have their neurotoxicities been evaluated in human neurobiology or in cells of the human central nervous system (CNS). In this paper we report the effects of added aluminum [sulfate; Al₂(SO₄)₃] and/or mercury [sulfate; HgSO4] to human neuronal-glial (HNG) cells in primary co-culture using the evolution of the pro-inflammatory transcription factor NF-kB (p50/p65) complex as a critical indicator for the onset of inflammatory neurodegeneration and pathogenic inflammatory signaling. As indexed by significant induction of the NF-kB (p50/p65) complex the results indicate: (i) a notable increase in pro-inflammatory signaling imparted by each of these two environmental neurotoxins toward HNG cells in the ambient 20-200 nM range; and (ii) a significant synergism in the neurotoxicity when aluminum (sulfate) and mercury (sulfate) were added together. This is the first report on the neurotoxic effects of aluminum sulfate and/or mercury sulfate on the initiation of inflammatory signaling in human brain cells in primary culture. The effects aluminum+mercury together on other neurologically important signaling molecules or the effects of other combinations of common environmental metallic neurotoxins to human neurobiology currently remain not well understood but certainly warrant additional investigation and further study in laboratory animals, in human primary tissue cultures of CNS cells, and in other neurobiologically realistic experimental test systems.