Transcriptomic and Quantitative Proteomic Analysis of Transporters and Drug Metabolizing Enzymes in Freshly Isolated Human Brain Microvessels
Copyright policy )Transcriptomic and Quantitative Proteomic Analysis of Transporters and Drug Metabolizing Enzymes in Freshly Isolated Human Brain Microvessels
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.
- University of Paris France
- Tohoku University Japan
- Centre Hospitalier Sainte-Anne France
- UNIVERSITE PARIS DESCARTES France
- Institut Cochin France
Proteomics, Glucose Transporter Type 1, ATP Binding Cassette Transporter, Subfamily B, Brain, In Vitro Techniques, Neoplasm Proteins, Excitatory Amino Acid Transporter 1, Glutamate Plasma Membrane Transport Proteins, Excitatory Amino Acid Transporter 2, Glutathione S-Transferase pi, Tandem Mass Spectrometry, Microvessels, ATP Binding Cassette Transporter, Subfamily G, Member 2, Humans, ATP-Binding Cassette Transporters, ATP Binding Cassette Transporter, Subfamily B, Member 1, Transcriptome, Chromatography, Liquid, Glutathione Transferase
Proteomics, Glucose Transporter Type 1, ATP Binding Cassette Transporter, Subfamily B, Brain, In Vitro Techniques, Neoplasm Proteins, Excitatory Amino Acid Transporter 1, Glutamate Plasma Membrane Transport Proteins, Excitatory Amino Acid Transporter 2, Glutathione S-Transferase pi, Tandem Mass Spectrometry, Microvessels, ATP Binding Cassette Transporter, Subfamily G, Member 2, Humans, ATP-Binding Cassette Transporters, ATP Binding Cassette Transporter, Subfamily B, Member 1, Transcriptome, Chromatography, Liquid, Glutathione Transferase
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