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标题：Identification of an exporter that regulates vitamin C supply from blood to the brain
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作者：Hiroshi Miyata ; Yu Toyoda ; Tappei Takada 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2022
卷号：25
期号：1
页码：1-17
DOI：10.1016/j.isci.2021.103642
语种：English
出版社：Elsevier
摘要：SummaryVitamin C (VC) distribution in our body requires VC transporters. However, mammalian VC exporters are yet to be identified. Herein, to unravel this long-standing mystery, we focused on the pathways whereby VC moves from blood to the brain, which should require a VC entrance and exit system composed of an importer and a latent exporter. Via cell-based transport analyses of VC efflux and using knockout mice generated via the CRISPR-Cas9 system, we identified GLUT12/SLC2A12 as a physiologically important VC efflux protein expressed in the choroid plexus;Glut12/Slc2a12knockout halved the cerebral VC levels, markedly increased VC accumulation in the choroid plexus, and reduced the cerebrospinal fluid VC levels. These findings facilitate our understanding of VC regulation and the physiological impact of VC in our body.Graphical abstractDisplay OmittedHighlights•A long-standing mystery in vitamin C handling in mammalians was uncovered•GLUT12 was identified as a physiologically important vitamin C efflux protein—VCEP•GLUT12 is expressed in the choroid plexus and acts as a vitamin C exporter•Glut12knockout halved the cerebral vitamin C levels in miceBiological sciences; Biochemistry; Molecular biology