Organotins disrupt components of glutamate homeostasis in rat astrocyte cultures
Organotins disrupt components of glutamate homeostasis in rat astrocyte cultures
复制标题
DOI：
10.1080/15287390151143668
复制
发表时间：
2001-06-22
影响因子：
2.6
通讯作者：
Eyer, CL
中科院分区：
文献类型：
--
作者：
Karpiak, VC;Bridges, RJ;Eyer, CL
本实验采用Arat皮层星形胶质细胞模型，研究了有机锡对星形胶质细胞谷氨酸调节的影响。星形胶质细胞暴露于低水平的有机锡产生显着的变化，在两个关键组成部分的谷氨酸稳态：谷氨酰胺合成酶（GS）的活性和高亲和力的L-谷氨酸转运。三甲基锡（TMT），三乙基锡（泰特），三苯基锡（TPT）表现出不同的能力，以减少GS活性和谷氨酸摄取。用1 μ M泰特或TPT孵育的培养物，而不是TMT，表现出GS活性的显著降低。暴露于泰特或TPT也产生谷氨酸转运活性的显著降低，而TMT未观察到。这些活性的下降不是由于细胞损失，如通过MTT还原和乳酸脱氢酶（LDH）泄漏所测量的。由于GS活性和转运蛋白活性的损失，没有看到与急性有机锡暴露，这是最有可能归因于一个完整的功能蛋白质的存在减少。虽然GS和谷氨酸转运体活性的衰减有机锡不匹配其神经毒性的模式，结果表明，潜在的亚毒性浓度的这些化合物，以增加细胞外谷氨酸和其他兴奋性毒性事件的相互作用。
Arat cortical astrocyte preparation was used to investigate the effects of organotins on glutamate regulation by astrocytes. Exposure of astrocytes to low levels of organotins produced significant changes in two key components of glutamate homeostasis: glutamine synthetase (GS) activity and the high-affinity transport of L-glutamate. Trimethyltin (TMT), triethyltin (TET), and triphenyltin (TPT) exhibited differential abilities to reduce GS activity and glutamate uptake. Cultures incubated with 1 muM TET or TPT, but not TMT, exhibited a marked decrease in GS activity. Exposure to TET or TPT also produced a significant decrease in glutamate transport activity that was not observed with TMT. These declines in activity were not attributable to cell loss as measured by MTT reduction and lactate dehydrogenase (LDH) leakage. Since the loss of GS activity and transporter activity was not seen with acute organotin exposure, it is most likely attributable to a decreased presence of fully functioning protein. While the attenuation of GS and glutamate transporter activities by organotins does not match their pattern of neurotoxicity, the results indicate the potential for subtoxic concentrations of these compounds to increase extracellular glutamate and interact with other excitotoxic episodes.