Manganese causes differential regulation of glutamate transporter (GLAST) taurine transporter and metallothionein in cultured rat astrocytes
Manganese causes differential regulation of glutamate transporter (GLAST) taurine transporter and metallothionein in cultured rat astrocytes
复制标题
DOI：
10.1016/s0161-813x(02)00012-8
复制
发表时间：
2002-10-01
期刊：
影响因子：
3.4
通讯作者：
Aschner, M
中科院分区：
文献类型：
--
作者：
Erikson, K;Aschner, M
由于环境（空气污染、土壤、水）和/或代谢异常（胆道排泄减少），可发生由过量脑锰（Mn）引起的神经毒性。锰与氧化应激以及神经递质代谢的改变有关，同时伴有神经行为缺陷。根据现有的少数对脑区域[Mn]进行检查的研究，在病理状态下，它可能达到100-500 muM。氨基酸（如天冬氨酸、谷氨酸、牛磺酸）以及二价金属（如锌、锰）的浓度由大脑中的星形胶质细胞调节。最近，有报道称，暴露于Mn的培养大鼠初级星形胶质细胞显示谷氨酸摄取减少，从而增加谷氨酸的兴奋毒性潜能。由于Mn在谷氨酸代谢方面的神经毒性机制尚不清楚，本研究的主要目的是将Mn暴露的星形胶质细胞中谷氨酸摄取的改变与谷氨酸转运体信息的改变联系起来。进一步，我们想检测金属硫蛋白（MT）和牛磺酸转运蛋白（tau-T）的基因表达作为锰暴露的标志物。谷氨酸摄取减少了近40%，谷氨酸/天冬氨酸转运体（GLAST） mRNA减少了48%。尽管tdu-T mRNA增加了123%，但牛磺酸摄取不受Mn暴露的影响。在这些Mn暴露的星形胶质细胞中，MT mRNA减少可能是由于金属代谢的改变，尽管尚未对此进行研究。这些数据表明，在Mn暴露的星形胶质细胞中，谷氨酸和牛磺酸的转运存在时间上的差异。(C) 2002爱思唯尔科学有限公司版权所有。
Neurotoxicity due to excessive brain manganese (Mn) can occur due to environmental (air pollution, soil, water) and/or metabolic aberrations (decreased biliary excretion). Manganese is associated with oxidative stress, as well as alterations in neurotransmitter metabolism with concurrent neurobehavioral deficits. Based on the few existing studies that have examined brain regional [Mn], it is likely that in pathological conditions it can reach 100-500 muM. Amino acid (e.g. aspartate, glutamate, taurine), as well as divalent metal (e.g. zinc, manganese) concentrations are regulated by astrocytes in the brain. Recently, it has been reported that cultured rat primary astrocytes exposed to Mn displayed decreased glutamate uptake, thereby, increasing the excitotoxic potential of glutamate. Since the neurotoxic mechanism(s) Mn employs in terms of glutamate metabolism is unknown, a primary goal of this study was to link altered glutamate uptake in Mn exposed astrocytes to alterations in glutamate transporter message. Further we wanted to examine the gene expression of metallothionein (MT) and taurine transporter (tau-T) as markers of Mn exposure. Glutamate uptake was decreased by nearly 40% in accordance with a 48% decrease in glutamate/aspartate transporter (GLAST) mRNA. Taurine uptake was unaffected by Mn exposure even though tdu-T mRNA increased by 123%. MT mRNA decreased in these Mn exposed astrocytes possibly due to altered metal metabolism, although this was not examined. These data show that glutamate and taurine transport in Mn exposed astrocytes are temporally different. (C) 2002 Elsevier Science Inc. All rights reserved.