Castro Maite A, Angulo Constanza, Brauchi Sebastián, Nualart Francisco, Concha Ilona I
Instituto de Bioquímica, Facultad de Ciencias, Universidad Austral de Chile, Valdivia, Chile.
Pflugers Arch. 2008 Nov;457(2):519-28. doi: 10.1007/s00424-008-0526-1. Epub 2008 May 28.
In this paper, we present a novel function for ascorbic acid. Ascorbic acid is an important water-soluble antioxidant and cofactor in various enzyme systems. We have previously demonstrated that an increase in neuronal intracellular ascorbic acid is able to inhibit glucose transport in cortical and hippocampal neurons. Because of the presence of sodium-dependent vitamin C transporters, ascorbic acid is highly concentrated in brain, testis, lung, and adrenal glands. In this work, we explored how ascorbic acid affects glucose and lactate uptake in neuronal and non-neuronal cells. Using immunofluorescence and reverse transcriptase-polymerase chain reaction (RT-PCR) analysis, the expression of glucose and ascorbic acid transporters in non-neuronal cells was studied. Like neurons, HEK293 cells expressed GLUT1, GLUT3, and SVCT2. With radioisotope-based methods, only intracellular ascorbic acid, but not extracellular, inhibits 2-deoxyglucose transport in HEK293 cells. As monocarboxylates such as pyruvate and lactate, are important metabolic sources, we analyzed the ascorbic acid effect on lactate transport in cultured neurons and HEK293 cells. Intracellular ascorbic acid was able to stimulate lactate transport in both cell types. Extracellular ascorbic acid did not affect this transport. Our data show that ascorbic acid inhibits glucose transport and stimulates lactate transport in neuronal and non-neuronal cells. Mammalian cells frequently present functional glucose and monocarboxylate transporters, and we describe here a general effect in which ascorbic acid functions like a glucose/monocarboxylate uptake switch in tissues expressing ascorbic acid transporters.
在本文中，我们展示了抗坏血酸的一种新功能。抗坏血酸是各种酶系统中一种重要的水溶性抗氧化剂和辅助因子。我们之前已经证明，神经元细胞内抗坏血酸的增加能够抑制皮质和海马神经元中的葡萄糖转运。由于存在钠依赖性维生素C转运体，抗坏血酸在脑、睾丸、肺和肾上腺中高度浓缩。在这项工作中，我们探讨了抗坏血酸如何影响神经元和非神经元细胞对葡萄糖和乳酸的摄取。利用免疫荧光和逆转录聚合酶链反应（RT-PCR）分析，研究了非神经元细胞中葡萄糖和抗坏血酸转运体的表达。与神经元一样，HEK293细胞表达GLUT1、GLUT3和SVCT2。采用基于放射性同位素的方法，只有细胞内抗坏血酸，而不是细胞外抗坏血酸，能抑制HEK293细胞中的2-脱氧葡萄糖转运。由于丙酮酸和乳酸等单羧酸是重要的代谢来源，我们分析了抗坏血酸对培养的神经元和HEK293细胞中乳酸转运的影响。细胞内抗坏血酸能够刺激这两种细胞类型中的乳酸转运。细胞外抗坏血酸不影响这种转运。我们的数据表明，抗坏血酸在神经元和非神经元细胞中抑制葡萄糖转运并刺激乳酸转运。哺乳动物细胞经常存在功能性葡萄糖和单羧酸转运体，我们在此描述了一种普遍效应，即抗坏血酸在表达抗坏血酸转运体的组织中起到类似葡萄糖/单羧酸摄取开关的作用。
