Transcriptomic and quantitative proteomic analysis of transporters and drug metabolizing enzymes in freshly isolated human brain microvessels

Ramzi Shawahna, Yasuo Uchida, Xavier Declèves, Sumio Ohtsuki, Salah Yousif, Sandrine Dauchy, Aude Jacob, Francine Chassoux, Catherine Daumas-Duport, Pierre Olivier Couraud, Tetsuya Terasaki, Jean Michel Scherrmann

Research output: Contribution to journalArticlepeer-review

232 Citations (Scopus)

Abstract

We have investigated the transcriptomic and/or proteomic patterns of 71 solute carrier (SLC) and organic solute (OST) transporters, 34 ATP-binding cassette (ABC) transporters, and 51 metabolizing enzymes in human brain microvessels. We used quantitative RT-PCR and LC-MS/MS to examine isolated brain microvessels and cortex biopsies from 12 patients with epilepsia or glioma. SLC2A1/GLUT1, SLC1A3/EAAT1, and SLC1A2/EAAT2 were the main SLC proteins whereas ABCG2/BCRP, ABCB1/MDR1, ABCA2 and ABCA8 were the main ABC quantified in isolated brain microvessels; ABCG2/BCRP was 1.6-fold more expressed than ABCB1/MDR1, and ABCC4/MRP4 was 10 times less abundant than ABCB1/MDR1. CYP1B1 and CYP2U1 were the only quantifiable CYPs. Finally, GSTP1, COMT, GSTM3, GSTO1 and GSTM2 proteins were the main phase II enzymes quantified; UGTs and NATs were not detected. Our extensive investigation of gene and protein patterns of transporters and metabolizing enzymes provides new molecular information for understanding drug entry and metabolism in the human blood-brain barrier.

Original languageEnglish
Pages (from-to)1332-1341
Number of pages10
JournalMolecular pharmaceutics
Volume8
Issue number4
DOIs
Publication statusPublished - 2011 Aug 1

Keywords

  • blood-brain barrier
  • drug-metabolizing enzymes
  • human
  • quantitative LC-MS/MS
  • transporters

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery

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