Department of Neurobiology, Key Laboratory of Medical Neurobiology of Ministry of Health of China, Zhejiang Province Key Laboratory of Neurobiology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, PR China.
Biochem Biophys Res Commun. 2011 Feb 25;405(4):691-6. doi: 10.1016/j.bbrc.2011.01.105. Epub 2011 Feb 1.
The astroglial cell-specific glutamate transporter subtype 2 (excitatory amino acid transporter 2, GLT1) plays an important role in excitotoxicity that develops after damage to the central nervous system (CNS) is incurred. Both the protein kinase C signaling pathway and the epidermal growth factor (EGF) pathway have been suggested to participate in the modulation of GLT1, but the modulatory mechanisms of GLT1 expression are not fully understood. In the present study, we aimed to evaluate the effects of insulin on GLT1 expression. We found that short-term stimulation of insulin led to the upregulation of both total and surface expressions of GLT1. Akt phosphorylation increased after insulin treatment, and triciribine, the inhibitor of Akt phosphorylation, significantly inhibited the effects of insulin. We also found that the upregulation of GLT1 expression correlated with increased kappa B motif-binding phosphoprotein (KBBP) and GLT1 mRNA levels. Our results suggest that insulin may modulate the expression of astrocytic GLT1, which might play a role in reactive astrocytes after CNS injuries.
星形胶质细胞特异性谷氨酸转运体亚型 2（兴奋性氨基酸转运体 2，GLT1）在中枢神经系统（CNS）损伤后发生的兴奋性毒性中发挥重要作用。蛋白激酶 C 信号通路和表皮生长因子（EGF）通路都被认为参与了 GLT1 的调节，但 GLT1 表达的调节机制尚不完全清楚。在本研究中，我们旨在评估胰岛素对 GLT1 表达的影响。我们发现，胰岛素的短期刺激导致 GLT1 的总表达和表面表达上调。胰岛素处理后 Akt 磷酸化增加，Akt 磷酸化抑制剂 triciribine 显著抑制了胰岛素的作用。我们还发现，GLT1 表达的上调与 kappa B 基序结合磷酸化蛋白（KBBP）和 GLT1 mRNA 水平的增加相关。我们的结果表明，胰岛素可能调节星形胶质细胞 GLT1 的表达，这可能在 CNS 损伤后的反应性星形胶质细胞中发挥作用。
