Qiu Shenfeng, Li Liying, Weeber Edwin J, May James M
Department Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
J Neurosci Res. 2007 Apr;85(5):1046-56. doi: 10.1002/jnr.21204.
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 ascorbate 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 ascorbate as a result of SVCT2 activity is crucial for neuronal development, functional maturation, and antioxidant responses.
神经元维持相对较高的细胞内抗坏血酸浓度，这主要通过钠依赖性维生素C转运体SVCT2的活性来实现。在这项研究中，我们研究了培养的神经元细胞转运和维持抗坏血酸盐的机制，以及该系统是否有助于神经元功能的成熟以及细胞对氧化应激和兴奋性毒性损伤的防御。我们发现，SVCT2有助于维持较高的细胞内抗坏血酸盐水平、正常的抗坏血酸盐转运动力学以及活性依赖性抗坏血酸盐循环。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降低。最后，来自SVCT2缺陷小鼠的海马培养物对氧化损伤和N-甲基-D-天冬氨酸诱导的兴奋性毒性表现出更高的易感性。我们的结果表明，由于SVCT2的活性而维持细胞内抗坏血酸盐对于神经元发育、功能成熟和抗氧化反应至关重要。
