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

doi:10.1021/mp200129p

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

PHA - Life and Pharmaceutical Science

Research output: Contribution to journal › Article › peer-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 language	English
Pages (from-to)	1332-1341
Number of pages	10
Journal	Molecular pharmaceutics
Volume	8
Issue number	4
DOIs	https://doi.org/10.1021/mp200129p
Publication status	Published - 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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Shawahna, R., Uchida, Y., Declèves, X., Ohtsuki, S., Yousif, S., Dauchy, S., Jacob, A., Chassoux, F., Daumas-Duport, C., Couraud, P. O., Terasaki, T., & Scherrmann, J. M. (2011). Transcriptomic and quantitative proteomic analysis of transporters and drug metabolizing enzymes in freshly isolated human brain microvessels. Molecular pharmaceutics, 8(4), 1332-1341. https://doi.org/10.1021/mp200129p

Transcriptomic and quantitative proteomic analysis of transporters and drug metabolizing enzymes in freshly isolated human brain microvessels. / Shawahna, Ramzi; Uchida, Yasuo; Declèves, Xavier; Ohtsuki, Sumio; Yousif, Salah; Dauchy, Sandrine; Jacob, Aude; Chassoux, Francine; Daumas-Duport, Catherine; Couraud, Pierre Olivier; Terasaki, Tetsuya; Scherrmann, Jean Michel.

In: Molecular pharmaceutics, Vol. 8, No. 4, 01.08.2011, p. 1332-1341.

Research output: Contribution to journal › Article › peer-review

Shawahna, R, Uchida, Y, Declèves, X, Ohtsuki, S, Yousif, S, Dauchy, S, Jacob, A, Chassoux, F, Daumas-Duport, C, Couraud, PO, Terasaki, T & Scherrmann, JM 2011, 'Transcriptomic and quantitative proteomic analysis of transporters and drug metabolizing enzymes in freshly isolated human brain microvessels', Molecular pharmaceutics, vol. 8, no. 4, pp. 1332-1341. https://doi.org/10.1021/mp200129p

Shawahna, Ramzi ; Uchida, Yasuo ; Declèves, Xavier ; Ohtsuki, Sumio ; Yousif, Salah ; Dauchy, Sandrine ; Jacob, Aude ; Chassoux, Francine ; Daumas-Duport, Catherine ; Couraud, Pierre Olivier ; Terasaki, Tetsuya ; Scherrmann, Jean Michel. / Transcriptomic and quantitative proteomic analysis of transporters and drug metabolizing enzymes in freshly isolated human brain microvessels. In: Molecular pharmaceutics. 2011 ; Vol. 8, No. 4. pp. 1332-1341.

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