Ascorbate transport by primary cultured neurons and its role in neuronal function and protection against excitotoxicity
Ascorbate transport by primary cultured neurons and its role in neuronal function and protection against excitotoxicity
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DOI：
10.1002/jnr.21204
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发表时间：
2007-04-01
影响因子：
4.2
通讯作者：
May, James M.
中科院分区：
文献类型：
--
作者：
Qiu, Shenfeng;Li, Liying;May, James M.
神经元维持细胞内相对较高的抗坏血酸浓度，这主要是通过钠依赖性维生素 C 转运蛋白 SVCT2 的活性来实现的。在这项工作中，我们研究了培养物中神经元细胞转运和维持抗坏血酸的机制，以及该系统是否有助于神经元功能成熟和细胞防御氧化应激和兴奋性毒性损伤。我们发现 SVCT2 有助于维持细胞内高抗坏血酸水平、正常的抗坏血酸转运动力学和活性依赖性抗坏血酸回收。免疫细胞化学研究表明，SVCT2 主要在培养的成熟海马神经元的轴突中表达。在缺乏 SVCT2 的情况下，海马神经元表现出神经突生长受阻、谷氨酸受体聚集减少以及自发神经元活动减少。最后，SVCT2 缺陷小鼠的海马培养物显示出对氧化损伤和 N-甲基-D-天冬氨酸诱导的兴奋性毒性的敏感性增加。我们的结果表明，SVCT2 活性导致细胞内 ascotbate 的维持对于神经元发育、功能成熟和抗氧化反应至关重要。 (c) 2007 年 Wiley-Liss, Inc.
Neurons maintain relatively high intracellular concentrations of ascorbic acid, which is achieved primarily by the activity of the sodium-dependent vitamin C transporter SVCT2. In this work, we studied the mechanisms by which neuronal cells in culture transport and maintain ascorbate as well as whether this system contributes to maturation of neuronal function and cellular defense against oxidative stress and excitotoxic injury. We found that the SVCT2 helps to maintain high intracellular ascotbate levels, normal ascorbate transport kinetics, and activity-dependent ascorbate recycling. Immunocytochemistry studies revealed that SVCT2 is expressed primarily in the axons of mature hippocampal neurons in culture. In the absence of SVCT2, hippocampal neurons exhibited stunted neurite outgrowth, less glutamate receptor clustering, and reduced spontaneous neuronal activity. Finally, hippocampal cultures from SVCT2-deficient mice showed increased susceptibility to oxidative damage and N-methyl-D-aspartate-induced excitotoxicity. Our results revealed that maintenance of intracellular ascotbate as a result of SVCT2 activity is crucial for neuronal development, functional maturation, and antioxiclant responses. (c) 2007 Wiley-Liss, Inc.