Transcriptomic and Quantitative Proteomic Analysis of Transporters and Drug Metabolizing Enzymes in Freshly Isolated Human Brain Microvessels

被引：288

作者：

Shawahna, Ramzi ^{[2
]}

Uchida, Yasuo ^{[3
]}

Decleves, Xavier ^{[1
,2
]}

Ohtsuki, Sumio ^{[3
]}

Yousif, Salah ^{[2
]}

Dauchy, Sandrine ^{[2
]}

Jacob, Aude ^{[2
]}

Chassoux, Francine ^{[4
]}

Daumas-Duport, Catherine ^{[4
]}

Couraud, Pierre-Olivier ^{[5
]}

Terasaki, Tetsuya ^{[3
]}

Scherrmann, Jean-Michel ^{[2
]}

机构：

[1] CNRS, INSERM, UMR 8206, Fac Pharm,U705, F-75006 Paris, France

[2] Univ Paris 05, Fac Pharm, Neuropsychopharmacol Addict CNRS UMR 8206, Paris, France

[3] Tohoku Univ, Grad Sch Pharmaceut Sci, Div Membrane Transport & Drug Targeting, Sendai, Miyagi 980, Japan

[4] Ste Anne Hosp, Paris, France

[5] INSERM, Inst Cochin, Dept Biol Cellulaire, U567, Paris, France

来源：

MOLECULAR PHARMACEUTICS | 2011年 / 8卷 / 04期

关键词：

blood-brain barrier; transporters; drug-metabolizing enzymes; human; quantitative LC-MS/MS; GLUTATHIONE-S-TRANSFERASE; CONSTITUTIVE ANDROSTANE RECEPTOR; PREGNANE-X RECEPTOR; UDP-GLUCURONOSYLTRANSFERASE; UP-REGULATION; RAT-BRAIN; P-GLYCOPROTEIN; BARRIER; EXPRESSION; PROTEINS;

D O I：

10.1021/mp200129p

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

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.

引用

页码：1332 / 1341

页数：10

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