Major involvement of Na+-dependent multivitamin transporter (SLC5A6/SMVT) in uptake of biotin and pantothenic acid by human brain capillary endothelial cells

Yasuo Uchida, Katsuaki Ito, Sumio Ohtsuki, Yoshiyuki Kubo, Takashi Suzuki, Tetsuya Terasaki

Research output: Contribution to journalArticlepeer-review

40 Citations (Scopus)

Abstract

The purpose of this study was to clarify the expression of Na+-dependent multivitamin transporter (SLC5A6/SMVT) and its contribution to the supply of biotin and pantothenic acid to the human brain via the blood-brain barrier. DNA microarray and immunohistochemical analyses confirmed that SLC5A6 is expressed in microvessels of human brain. The absolute expression levels of SLC5A6 protein in isolated human and monkey brain microvessels were 1.19 and 0.597 fmol/μg protein, respectively, as determined by a quantitative targeted absolute proteomics technique. Using an antibody-free method established by Kubo et al. (2015), we found that SLC5A6 was preferentially localized at the luminal membrane of brain capillary endothelium. Knock-down analysis using SLC5A6 siRNA showed that SLC5A6 accounts for 88.7% and 98.6% of total [3H]biotin and [3H]pantothenic acid uptakes, respectively, by human cerebral microvascular endothelial cell line hCMEC/D3. SLC5A6-mediated transport in hCMEC/D3 was markedly inhibited not only by biotin and pantothenic acid, but also by prostaglandin E2, lipoic acid, docosahexaenoic acid, indomethacin, ketoprofen, diclofenac, ibuprofen, phenylbutazone, and flurbiprofen. This study is the first to confirm expression of SLC5A6 in human brain microvessels and to provide evidence that SLC5A6 is a major contributor to luminal uptake of biotin and pantothenic acid at the human blood-brain barrier.

Original languageEnglish
Pages (from-to)97-112
Number of pages16
JournalJournal of Neurochemistry
Volume134
Issue number1
DOIs
Publication statusPublished - 2015 Jul 1

Keywords

  • SLC5A6
  • biotin
  • human blood-brain barrier
  • luminal uptake
  • pantothenic acid
  • structure of inhibitor

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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