Identification of an exporter that regulates vitamin C supply from blood to the brain

Hiroshi Miyata; Yu Toyoda; Tappei Takada; Toshimitsu Hiragi; Yu Kubota; Ryuichiro Shigesawa; Ryuta Koyama; Yuji Ikegaya; Hiroshi Suzuki

doi:10.1016/j.isci.2021.103642

Identification of an exporter that regulates vitamin C supply from blood to the brain

iScience. 2022 Jan 13;25(1):103642. doi: 10.1016/j.isci.2021.103642. eCollection 2022 Jan 21.

Authors

Hiroshi Miyata¹, Yu Toyoda¹, Tappei Takada¹, Toshimitsu Hiragi², Yu Kubota¹, Ryuichiro Shigesawa¹, Ryuta Koyama², Yuji Ikegaya², Hiroshi Suzuki¹

Affiliations

¹ Department of Pharmacy, The University of Tokyo Hospital, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
² Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.

Abstract

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; Glut12/Slc2a12 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.

Keywords: Biochemistry; Biological sciences; Molecular biology.