Cystine/Glutamate Exchange Transport System in Brain

发现大鼠胶质瘤C-6细胞和新生大鼠大脑半球培养的星形胶质细胞对谷氨酸的摄取是由谷氨酸/天冬氨酸系统（system X^-_）和胱氨酸/谷氨酸交换系统（system X^-_）介导的。在C-6细胞中，在0.05 mM谷氨酸时，通过X^-_系统和X^-_系统的谷氨酸摄取分别约占总摄取的35%和55%。在培养的星形胶质细胞中，通过X^-_系统摄取谷氨酸非常有效，而通过X^-_系统摄取谷氨酸相对较弱，其对谷氨酸总摄取的贡献几乎可以忽略不计。然而，在C-6细胞和星形胶质细胞中，系统x^-_是摄取胱氨酸所必需的。培养基中的胱氨酸是谷胱甘肽的重要前体，通过x^-_系统对胱氨酸摄取的抑制导致谷胱甘肽的严重缺乏。胎鼠（孕16天）的脑细胞显示出系统x^-_活性。这些细胞经培养后分化为神经元样细胞和星形细胞样细胞。星形细胞样细胞的x^-_系统活性高，而神经元样细胞的x^-_系统活性低。与星形细胞样细胞共培养时，神经元样细胞的谷胱甘肽水平保持不变，但与星形细胞样细胞分离后，谷胱甘肽水平下降。提示星形胶质细胞通过x^-_系统摄取胱氨酸并将其还原为半胱氨酸，半胱氨酸从细胞中释放出来，被神经元利用以维持其谷胱甘肽水平。

The uptake of glutamate in rat glioma C-6 cells and cultured astrocytes derived from newborn rat cerebral hemispheres was found to be mediated by glutamate/aspartate system (System X^-_) and cystine/glutamate exchange system (System x^-_). In C-6 cells the glutamate uptake via System X^-_ and x^-_ approximately accounted for 35% and 55% of the total uptake, respectively, at 0.05 mM glutamate. In cultured astrocytes the glutamate uptake via System X^-_ was very potent, whereas the uptake vis System x^-_ was relatively weak and its contribution to the total uptake of glutamate seemed almost negligible. However, in both C-6 cells and astrocytes System x^-_ was necessary for the uptake of cystine. Cystine in the culture medium was an essential precursor of glutathione and the inhibition of the cystine uptake via System x^-_ led to a severe deficiency in glutathione. Brain cells prepared from fetal rat (16 days gestation) showed a System x^-_ activity. These cells differentiated to neuron-like cells and astrocyte-like cells when cultured. Astrocyte-like cells showed a high activity of System x^-_ whereas neuron-like cells showed a very low activity. A glutathione level of neuron-like cells was maintained when they were co-cultured with astrocyte-like cells, but the level went down when they were separated from astrocyte-like cells. It was suggested that astrocytes took up cystine via System x^-_ and reduced it to cysteine, which was released from the cells and utilized by neurons to maintain their glutathione level.