Quantitative targeted absolute proteomics of human blood-brain barrier transporters and receptors

Yasuo Uchida, Sumio Ohtsuki, Yuki Katsukura, Chiemi Ikeda, Takashi Suzuki, Junichi Kamiie, Tetsuya Terasaki

Research output: Contribution to journalArticle

442 Citations (Scopus)

Abstract

We have obtained, for the first time, a quantitative protein expression profile of membrane transporters and receptors in human brain microvessels, that is, the blood-brain barrier (BBB). Brain microvessels were isolated from brain cortexes of seven males (16-77 years old) and protein expression of 114 membrane proteins was determined by means of a liquid chromatography - tandem mass spectrometric quantification method using recently established in-silico peptide selection criteria. Among drug transporters, breast cancer resistance protein showed the most abundant protein expression (8.14 fmol/lg protein), and its expression level was 1.85-fold greater in humans than in mice. By contrast, the expression level of P-glycoprotein in humans (6.06 fmol/lg protein) was 2.33-fold smaller than that of mdr1a in mice. The organic anion transporters reported in rodent BBB, that is, multidrug resistance-associated protein, organic anion transporter and organic anion-transporting polypeptide family members, were under limit of quantification in humans, except multidrug resistance-associated protein 4 (0.195 fmol/lg protein). Among detected transporters and receptors for endogenous substances, the glucose transporter 1 level was similar to that of mouse, while the L-type amino acid transporter 1 level was fivefold smaller than that of mouse. These findings should be useful for understanding human BBB function and its differences from that in mouse.

Original languageEnglish
Pages (from-to)333-345
Number of pages13
JournalJournal of Neurochemistry
Volume117
Issue number2
DOIs
Publication statusPublished - 2011 Apr 1

Keywords

  • Human blood-brain barrier
  • Liquid chromatography-tandem mass spectrometry
  • Quantitative targeted absolute proteomics
  • Receptors
  • Species difference
  • Transporters

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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