Glutamate transporter expression and function in a striatal neuronal model of Huntington's disease.
Glutamate transporter expression and function in a striatal neuronal model of Huntington's disease.
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DOI：
10.1016/j.neuint.2013.02.026
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发表时间：
2013-06
影响因子：
4.2
通讯作者：
Rosenberg PA
中科院分区：
文献类型：
--
作者：
Petr GT;Bakradze E;Frederick NM;Wang J;Armsen W;Aizenman E;Rosenberg PA
兴奋性毒性可能与亨廷顿氏病的发病机制有关。高亲和力Na+依赖的谷氨酸转运体，驻留在质膜上，清除细胞外空间的谷氨酸，是预防兴奋性毒性的主要手段。许多报道表明，亨廷顿氏病与谷氨酸转运蛋白的表达和功能下降有关。我们研究了这些转运体在亨廷顿病细胞模型STHdhQ111/Q111和STHdhQ7/Q7细胞中的表达和功能。我们发现只有GLT-1b和EAAC1在这些细胞系中表达，并且只有EAAC1对谷氨酸摄取有显著贡献。令人惊讶的是，STHdhQ111/Q111细胞中Na+依赖性谷氨酸摄取的增加伴随着EAAC1表面表达的增加。我们研究了Akt通路对EAAC1介导摄取的影响，因为EAAC1表面表达受Akt的影响，并且先前的研究表明Akt在STHdhQ111/Q111细胞中表达增加。Akt通路抑制剂抑制了STHdhQ7/Q7和STHdhQ111/Q111细胞系的谷氨酸摄取，事实上，在我们的培养条件下，我们发现两种细胞系之间的Akt激活没有差异。因此，Akt激活的差异似乎不能解释STHdhQ111/Q111细胞中EAAC1介导的摄取增加。
Excitotoxicity may contribute to the pathogenesis of Huntington’s disease. High affinity Na+ dependent glutamate transporters, residing in the plasma membrane, clear glutamate from the extracellular space and are the primary means of prevention against excitotoxicity. Many reports suggest that Huntington’s disease is associated with a decrease in the expression and function of glutamate transporters. We studied the expression and function of these transporters in a cellular model of Huntington’s disease, STHdhQ111/Q111 and STHdhQ7/Q7 cells. We found that only GLT-1b and EAAC1 were expressed in these cell lines and only EAAC1 significantly contributed to the glutamate uptake. Surprisingly, there was an increase in Na+-dependent glutamate uptake in STHdhQ111/Q111 cells accompanied by an increase in surface expression of EAAC1 We studied the influence of the Akt pathway on EAAC1 mediated uptake, since EAAC1 surface expression is influenced by Akt and previous studies have shown increased Akt expression in STHdhQ111/Q111 cells. Glutamate uptake was inhibited by Akt pathway inhibitors in both the STHdhQ7/Q7 and the STHdhQ111/Q111 cell lines, and, in fact, we have found no difference in Akt activation between the two cell lines under our conditions of culture. Therefore a difference in Akt activation does not seem to explain the increase in EAAC1 mediated uptake in the STHdhQ111/Q111 cells.
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DOI：
10.1523/jneurosci.6129-08.2009
发表时间：
2009-06-17
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
DeSilva TM;Kabakov AY;Goldhoff PE;Volpe JJ;Rosenberg PA
通讯作者：
Rosenberg PA
影响因子：
6.1
作者：
Huang, Kun;Kang, Martin H.;Hayden, Michael R.
通讯作者：
Hayden, Michael R.
影响因子：
64.8
作者：
KANAI, Y;HEDIGER, MA
通讯作者：
HEDIGER, MA
影响因子：
25
作者：
Aoyama, K;Suh, SW;Swanson, RA
通讯作者：
Swanson, RA
影响因子：
16.2
作者：
Gunawardena, S;Her, LS;Goldstein, LSB
通讯作者：
Goldstein, LSB