Alteration of the glutamate and GABA transporters in the hippocampus of the Niemann-Pick disease, type C mouse using proteomic analysis
Alteration of the glutamate and GABA transporters in the hippocampus of the Niemann-Pick disease, type C mouse using proteomic analysis
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DOI：
10.1002/pmic.200500412
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发表时间：
2006-02-01
期刊：
影响因子：
3.4
通讯作者：
Lee, B
中科院分区：
文献类型：
--
作者：
Byun, K;Kim, J;Lee, B
C 型尼曼-匹克病 (NPC) 是一种致命的常染色体隐性遗传胆固醇疾病，其特征是严重的进行性神经变性。为了揭示神经变性的机制，对 NPC -/- 小鼠的海马体应用了蛋白质组学和形态学方法。利用 Two-DE 解析 4 周和 8 周龄 NPC +/+ 和 -/- 小鼠的海马蛋白表达谱。通过MALDI-TOF MS和数据库搜索鉴定差异表达蛋白点。 4 周龄时，NPC +/+ 和 -/- 小鼠之间的蛋白质谱没有显着差异。然而，在8周龄时，NPC +/+和-/-小鼠的蛋白质表达出现显着差异。其中，谷氨酸受体2前体被鉴定出来。神经转运蛋白的免疫组织化学研究表明，4周龄和8周龄NPC -/- 小鼠中胶质GABA转运蛋白（GAT-3）均增加，8周龄NPC -/- 小鼠中谷氨酸脱羧酶（GAD-6）增加。 8 周大的 NPC -/- 小鼠中神经胶质谷氨酸转运蛋白、兴奋性氨基酸载体 1 (EAAC1) 减少。总之，我们的数据可以通过扰动鼻咽癌单基因敲除模型中的蛋白质网络和神经转运系统来了解基本机制。
Niemann-Pick disease type C (NPC) is a fatal autosomal recessive cholesterol disorder characterized by severe progressive neurodegeneration. To unveil the mechanism of neurodegeneration, proteomic and morphological approaches were applied to the hippocampus in NPC -/- mouse. Two-DE was utilized to resolve the hippocampal protein expression profiles of 4- and 8-week-old NPC +/+ and -/- mice. Differentially expressed protein spots were identified by MALDI-TOF MS and database searching. At 4 weeks of age, there was no significant difference in protein profiles between NPC +/+ and -/- mice. However, at the age of 8 weeks, NPC +/+ and -/- mice showed marked difference in protein expressions. Among these, glutamate receptor 2 precursor was identified. The immunohistochemical study on neurotransporters showed that glial GABA transporter (GAT-3) increased in both 4- and 8-week-old NPC -/- mouse and glutamic acid decarboxylase (GAD-6) increased in 8-week-old NPC -/- mouse. Glial glutamate transporter, excitatory amino acids carrier-1 (EAAC1), decreased in 8-week-old NPC -/- mouse. In conclusion, our data may provide insight into the understanding of the basic mechanism through perturbation of protein networks and neurotransporter systems in a single gene knockout model of NPC disease.