| Autor: |
Dehouck MP; Univ. Artois, UR 2465, Laboratoire de la Barrière Hémato-Encéphalique (LBHE), F-62300 Lens, France., Tachikawa M; Graduate School of Biomedical Sciences, Tokushima University, 1-78-1 Shomachi, Tokushima 770-8505, Japan.; Division of Membrane Transport and Drug Targeting, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8577, Japan., Hoshi Y; Division of Membrane Transport and Drug Targeting, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8577, Japan., Omori K; Division of Membrane Transport and Drug Targeting, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8577, Japan., Maurage CA; Pathology Department, CHRU Lille, 59037 Lille, France., Strecker G; Intensive Care Unit, CHRU Lille, 59037 Lille, France., Dehouck L; Univ. Artois, UR 2465, Laboratoire de la Barrière Hémato-Encéphalique (LBHE), F-62300 Lens, France., Boucau MC; Univ. Artois, UR 2465, Laboratoire de la Barrière Hémato-Encéphalique (LBHE), F-62300 Lens, France., Uchida Y; Division of Membrane Transport and Drug Targeting, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8577, Japan., Gosselet F; Univ. Artois, UR 2465, Laboratoire de la Barrière Hémato-Encéphalique (LBHE), F-62300 Lens, France., Terasaki T; Division of Membrane Transport and Drug Targeting, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8577, Japan.; School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, FI-70211 Kuopio, Finland., Karamanos Y; Univ. Artois, UR 2465, Laboratoire de la Barrière Hémato-Encéphalique (LBHE), F-62300 Lens, France. |
| Abstrakt: |
We previously developed an in vitro model of the human blood-brain barrier (BBB) based on the use of endothelial cells derived from CD34 + -hematopoietic stem cells and cultured with brain pericytes. The purpose of the present study was to provide information on the protein expression levels of the transporters, receptors, tight junction/adherence junction molecules, and transporter-associated molecules of human brain-like endothelial cells (hBLECs). The absolute protein expression levels were determined by liquid chromatography-mass spectrometry-based quantitative targeted absolute proteomics and compared with those from human brain microvessels (hBMVs). The protein levels of CD144, CD147, MRP4, Annexin A6 and caveolin-1 showed more than 3-fold abundance in hBLECs, those of MCT1, Connexin 43, TfR1, and claudin-5 showed less than 3-fold differences, and the protein levels of other drug efflux transporters and nutrient transporters were less represented in hBLECs than in hBMVs. It is noteworthy that BCRP was more expressed than MDR1 in hBLECs, as this was the case for hBMVs. These results suggest that transports mediated by MCT1, TfR1, and claudin-5-related tight junction function reflect the in vivo BBB situation. The present study provided a better characterization of hBLECs and clarified the equivalence of the transport characteristics between in vitro BBB models and in vivo BBB models using LC-MS/MS-based protein quantification. |
