Department of Neurology, Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
Basic Clin Pharmacol Toxicol. 2013 Jan;112(1):19-24. doi: 10.1111/bcpt.12011. Epub 2012 Nov 30.
Glutamate transporter-1 (GLT-1) plays a dual role in glutamate transportation: both normally devotion to the clearance of glutamate and during some pathological conditions extruding glutamate to the extracellular space. Therefore, it is uncertain whether increased expression of GLT-1 will actually be helpful against glutamate excitotoxicity. In this study, GLT-1 up-regulation was induced by ceftriaxone, and L-glutamate was added to induce glutamate toxicity in primary cultured rat cortical cells. The results showed that up-regulated GLT-1 induced by 1 μM ceftriaxone for 2 days markedly increased cell viability, decreased apoptotic cell death and alleviated ultrastructural damage induced by 50 μM glutamate 15 min. as well as promoted L-[(3) H]-glutamate uptake in cultured cells. GLT-1 up-regulation had no effect on the intracellular free calcium concentration (Ca(2+) ) in the resting situation, while relieved intracellular calcium overloading by reducing the elevation and promoting the recovery of Ca(2+) following stimulation of 50 μM glutamate for 2 min. Applying 100 μM dihydrokainic acid (GLT-1 antagonist) 30 sec. before glutamate eliminated the above effect of GLT-1 up-regulation on Ca(2+) . In conclusion, GLT-1 up-regulation induced by ceftriaxone plays a positive glutamate transporting role against glutamate toxicity in primary cultured rat cortical cells.
谷氨酸转运体-1（GLT-1）在谷氨酸转运中具有双重作用：正常情况下负责清除谷氨酸，在某些病理条件下将谷氨酸外排到细胞外间隙。因此，增加 GLT-1 的表达实际上是否有助于对抗谷氨酸兴奋性毒性还不确定。在这项研究中，用头孢曲松诱导 GLT-1 上调，并用 L-谷氨酸诱导原代培养的大鼠皮质细胞产生谷氨酸毒性。结果表明，用 1 μM 头孢曲松诱导 2 天可显著上调 GLT-1，增加细胞活力，减少凋亡细胞死亡，并减轻 50 μM 谷氨酸 15 分钟诱导的超微结构损伤，同时促进培养细胞中 L-[(3) H]-谷氨酸摄取。GLT-1 上调对静息状态下的细胞内游离钙浓度 (Ca(2+) )没有影响，但通过减少谷氨酸刺激 2 分钟后 Ca(2+) 的升高并促进其恢复，缓解细胞内钙超载。在谷氨酸刺激前 30 秒应用 100 μM 二氢酮酸（GLT-1 拮抗剂）可消除 GLT-1 上调对 Ca(2+) 的上述作用。总之，头孢曲松诱导的 GLT-1 上调在原代培养的大鼠皮质细胞中对谷氨酸毒性具有积极的谷氨酸转运作用。
