Ascorbic acid participates in a general mechanism for concerted glucose transport inhibition and lactate transport stimulation
Ascorbic acid participates in a general mechanism for concerted glucose transport inhibition and lactate transport stimulation
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DOI：
10.1007/s00424-008-0526-1
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发表时间：
2008-11-01
影响因子：
4.5
通讯作者：
Concha, Ilona I.
中科院分区：
文献类型：
--
作者：
Castro, Maite A.;Angulo, Constanza;Concha, Ilona I.
在本文中，我们提出了一种新的抗坏血酸功能。抗坏血酸是多种酶系统中重要的水溶性抗氧化剂和辅因子。我们先前已经证明，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运输。由于钠依赖的维生素C转运体的存在，抗坏血酸在大脑、睾丸、肺和肾上腺中高度集中。在这项工作中，我们探索了抗坏血酸如何影响神经细胞和非神经细胞对葡萄糖和乳酸的摄取。应用免疫荧光和逆转录聚合酶链式反应(RT-PCR)分析非神经细胞葡萄糖和抗坏血酸转运蛋白的表达。与神经元一样，HEK293细胞表达GLUT1、GLUT3和SVCT2。在基于放射性同位素的方法中，只有细胞内的抗坏血酸而不是细胞外的抗坏血酸抑制HEK293细胞中2-脱氧葡萄糖的转运。由于丙酮酸和乳酸等单羧酸盐是重要的代谢来源，我们分析了抗坏血酸对培养神经元和HEK293细胞乳酸转运的影响。细胞内抗坏血酸能够刺激两种细胞的乳酸运输。细胞外抗坏血酸不影响这种转运。我们的数据显示，抗坏血酸抑制神经细胞和非神经细胞中葡萄糖的运输，刺激乳酸的运输。哺乳动物细胞经常存在功能性葡萄糖和单羧酸转运体，我们在这里描述了抗坏血酸在表达抗坏血酸转运体的组织中的作用，就像葡萄糖/单羧酸摄取开关一样。
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.