Vitamin C crosses the blood-brain barrier in the oxidized form through the glucose transporters

被引:251
作者
Agus, DB
Gambhir, SS
Pardridge, WM
Spielholz, C
Baselga, J
Vera, JC
Golde, DW
机构
[1] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA
[2] Univ Calif Los Angeles, Sch Med, Brain Res Inst, Dept Med, Los Angeles, CA 90095 USA
[3] Univ Calif Los Angeles, Sch Med, Crump Inst Biol Imaging, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA
[4] Hosp Gen Valle Hebron, Barcelona 08035, Spain
关键词
ascorbic acid; dehydroascorbic acid; GLUT1; neurodegenerative disease; antioxidants;
D O I
10.1172/JCI119832
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Vitamin C concentrations in the brain exceed those in blood by 10-fold. In both tissues, the vitamin is present primarily in the reduced form, ascorbic acid. We identified the chemical form of vitamin C that readily crosses the blood-brain barrier, and the mechanism of this process. Ascorbic acid was not able to cross the blood-brain barrier in our studies. In contrast, the oxidized form of vitamin C, dehydroascorbic acid (oxidized ascorbic acid), readily entered the brain and was retained in the brain tissue in the form of ascorbic acid, Transport of dehydroascorbic acid into the brain was inhibited by D-glucose, but not by L-glucose. The facilitative glucose transporter, GLUT1, is expressed on endothelial cells at the blood-brain barrier, and is responsible far glucose entry into the brain, This study provides evidence showing that GLUT1 also transports dehydroascorbic acid Into the brain. The findings define the transport of dehydroascorbic acid by GLUT1 as a mechanism by which the brain acquires vitamin C, and point to the oxidation of ascorbic acid as a potentially important regulatory step in accumulation of the vitamin by the brain. These results have implications for increasing antioxidant potential in the central nervous system.
引用
收藏
页码:2842 / 2848
页数:7
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