Vitamin C uptake and recycling among normal and tumor cells from the central nervous system
Vitamin C uptake and recycling among normal and tumor cells from the central nervous system
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DOI：
10.1002/jnr.20326
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发表时间：
2005-01-01
影响因子：
4.2
通讯作者：
Nualart, F
中科院分区：
文献类型：
--
作者：
Astuya, A;Caprile, T;Nualart, F
特化细胞使用钠依赖性协同转运蛋白（SVCT 1和SVCT 2）以还原形式转运维生素C。此外，不同的细胞通过葡萄糖转运蛋白（GLUT）转运氧化形式的维生素C，脱氢抗坏血酸。我们最近提出了一个模型，维生素C的摄取，解决了明显的矛盾，虽然只有抗坏血酸是可检测的体内，有细胞，运输只有脱氢抗坏血酸。我们进行了详细的动力学分析，以比较正常人黑素细胞，从大脑皮层分离的神经元，下丘脑室管膜胶质细胞和星形胶质细胞的维生素C摄取的机制。还在人少突胶质细胞瘤细胞系TC 620、人脉络丛乳头状瘤细胞（HCPPC-1）和神经母细胞瘤细胞系Neuro-2a中分析了抗坏血酸的摄取。黑素细胞被用来进行维生素C摄取的详细分析。运输数据的Lineweaver-Burk图分析揭示了一个功能性成分（K-m 20 μ M）的存在下，参与抗坏血酸运输的黑色素细胞。在神经元和下丘脑伸长细胞中也观察到维生素C钠依赖性饱和摄取。我们通过原位杂交证实了SVCT 2在神经元中的表达;然而，在星形胶质细胞中原位未检测到SVCT 2的表达。功能数据表明，星形胶质细胞运输主要是脱氢抗坏血酸，使用葡萄糖转运蛋白GLUT 1。我们的功能性摄取分析支持星形胶质细胞参与神经系统中维生素C循环的假设。这种循环模式可以作为一个有效的系统，通过避免抗氧化保护产生的脱氢抗坏血酸的水解维生素C的救助。(C)2004 Wiley-Liss，Inc.
Specialized cells transport vitamin C in its reduced form using sodium-dependent cotransporters (SVCT1 and SVCT2). Additionally, different cells transport the oxidized form of vitamin C, dehydroascorbic acid, through glucose transporters (GLUTs). We have proposed recently a model for vitamin C uptake that resolves the apparent contradiction that although only ascorbic acid is detectable in vivo, there are cells that transport only dehydroascorbic acid. We carried out a detailed kinetic analysis to compare the mechanisms of vitamin C uptake in normal human melanocytes, neurons isolated from brain cortex, hypothalamic ependymal-glial cells, and astrocytes. Uptake of ascorbic acid was also analyzed in the human oligodendroglioma cell line TC620, in human choroid plexus papilloma cells (HCPPC-1), and in the neuroblastoma cell line Neuro-2a. Melanocytes were used to carry out a detailed analysis of vitamin C uptake. Analysis of the transport data by the Lineweaver-Burk plot revealed the presence of one functional component (K-m 20 muM) involved in ascorbic acid transport by melanocytes. Vitamin C sodium-dependent saturable uptake was also observed in neurons and hypothalamic tanycytes. We confirmed SVCT2 expression in neurons by in situ hybridization; however, SVCT2 expression was not detected in astrocytes in situ. Functional data indicate that astrocytes transport mainly dehydroascorbic acid, using the glucose transporter GLUT1. Our functional uptake analyses support the hypothesis that astrocytes are involved in vitamin C recycling in the nervous system. This recycling model may work as an efficient system for the salvage of vitamin C by avoiding the hydrolysis of dehydroascorbic acid produced by antioxidative protection. (C) 2004 Wiley-Liss, Inc.