Miyata Hiroshi, Toyoda Yu, Takada Tappei, Hiragi Toshimitsu, Kubota Yu, Shigesawa Ryuichiro, Koyama Ryuta, Ikegaya Yuji, Suzuki Hiroshi
Department of Pharmacy, The University of Tokyo Hospital, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
iScience. 2022 Jan 13;25(1):103642. doi: 10.1016/j.isci.2021.103642. eCollection 2022 Jan 21.
Vitamin 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; knockout 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.
我们体内维生素C(VC)的分布需要VC转运蛋白。然而,哺乳动物的VC输出蛋白尚未被鉴定出来。在此,为了解开这个长期存在的谜团,我们专注于VC从血液进入大脑的途径,这应该需要一个由进口蛋白和潜在输出蛋白组成的VC进出系统。通过基于细胞的VC外排转运分析,并使用通过CRISPR-Cas9系统产生的基因敲除小鼠,我们鉴定出GLUT12/SLC2A12是一种在脉络丛中表达的具有重要生理意义的VC外排蛋白;基因敲除使大脑VC水平减半,显著增加了脉络丛中VC的积累,并降低了脑脊液中的VC水平。这些发现有助于我们理解VC的调节以及VC在我们体内的生理影响。