ACS Publications. Most Trusted. Most Cited. Most Read

OR SEARCH CITATIONS

My Activity
Publications
CONTENT TYPES

Figure 1Loading Img
Download Hi-Res ImageDownload to MS-PowerPointCite This:Mol. Pharmaceutics 2013, 10, 1, 289-296
RETURN TO ISSUEPREVArticleNEXT

Quantitative Targeted Absolute Proteomic Analysis of Transporters, Receptors and Junction Proteins for Validation of Human Cerebral Microvascular Endothelial Cell Line hCMEC/D3 as a Human Blood–Brain Barrier Model

View Author Information
† Division of Membrane Transport and Drug Targeting, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan
‡ Department of Pharmaceutical Microbiology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan
§ INSERM, U1016, Institut Cochin, Paris, France
∥ CNRS, UMR8104, Paris, France
⊥ Université Paris Descartes, Paris, France
# Neuropsychopharmacologie des addictions (CNRS UMR 8206), Université Paris Descartes, Faculté de Pharmacie, Paris, France
○ INSERM U705, Neuropsychopharmacologie des addictions, Paris, France
*Division of Membrane Transport and Drug Targeting, Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aoba, Aramaki, Aoba-ku, Sendai 980-8578, Japan. Tel: +81-22-795-6831. Fax: +81-22-795-6886. E-mail: [email protected]
Cite this: Mol. Pharmaceutics 2013, 10, 1, 289–296
Publication Date (Web):November 8, 2012
https://doi.org/10.1021/mp3004308
Copyright © 2012 American Chemical Society
RIGHTS & PERMISSIONS

Article Views

5236

Altmetric

-

Citations

167
LEARN ABOUT THESE METRICS
Read OnlinePDF (510 KB)
Get e-Alerts
SUBJECTS:

Abstract

Abstract Image

Human cerebral microvascular endothelial cell line hCMEC/D3 is an established model of the human blood–brain barrier (BBB). The purpose of the present study was to determine, by means of quantitative targeted absolute proteomics, the protein expression levels in hCMEC/D3 cells of multiple transporters, receptors and junction proteins for comparison with our previously reported findings in isolated human brain microvessels. Among 91 target molecules, 12 transporters, 2 receptors, 1 junction protein and 1 membrane marker were present at quantifiable levels in plasma membrane fraction of hCMEC/D3 cells. ABCA2, MDR1, MRP4, BCRP, GLUT1, 4F2hc, MCT1, ENT1, transferrin and insulin receptors and claudin-5 were detected in both hCMEC/D3 cells and human brain microvessels. After normalization based on Na+/K+ ATPase expression, the differences in protein expression levels between hCMEC/D3 cells and human brain microvessels were within 4-fold for these proteins, with the exceptions of ENT1, transferrin receptor and claudin-5. ABCA8, LAT1, LRP1 and γ-GTP were below the limit of quantification in the cells, but were found in human brain microvessels. ABCA3, ABCA6, MRP1 and ATA1 were found only in hCMEC/D3 cells. Furthermore, compared with human umbilical vein endothelial cells (HUVECs) as reference nonbrain endothelial cells, MDR1 was found only in hCMEC/D3 cells, and GLUT1 expression was 15-fold higher in hCMEC/D3 cells than in HUVECs. In conclusion, this is the first study to examine the suitability and limitations of the hCMEC/D3 cell line as a BBB functional model in terms of quantitative expression levels of transporters, receptors and tight junction proteins.

KEYWORDS:

Cited By

This article is cited by 167 publications.

  1. Ryotaro Yagi, Takeshi Masuda, Seiryo Ogata, Ayano Mori, Shingo Ito, Sumio Ohtsuki. Proteomic Evaluation of Plasma Membrane Fraction Prepared from a Mouse Liver and Kidney Using a Bead Homogenizer: Enrichment of Drug-Related Transporter Proteins. Molecular Pharmaceutics 2020, 17 (11) , 4101-4113. https://doi.org/10.1021/acs.molpharmaceut.0c00547
  2. Elena Puris, Mikko Gynther, Elizabeth C.M. de Lange, Seppo Auriola, Margareta Hammarlund-Udenaes, Kristiina M. Huttunen, Irena Loryan. Mechanistic Study on the Use of the l-Type Amino Acid Transporter 1 for Brain Intracellular Delivery of Ketoprofen via Prodrug: A Novel Approach Supporting the Development of Prodrugs for Intracellular Targets. Molecular Pharmaceutics 2019, 16 (7) , 3261-3274. https://doi.org/10.1021/acs.molpharmaceut.9b00502
  3. Takeshi Masuda, Toshiki Hoshiyama, Tatsuki Uemura, Mio Hirayama-Kurogi, Seiryo Ogata, Arisu Furukawa, Pierre-Olivier Couraud, Tomomi Furihata, Shingo Ito, Sumio Ohtsuki. Large-Scale Quantitative Comparison of Plasma Transmembrane Proteins between Two Human Blood–Brain Barrier Model Cell Lines, hCMEC/D3 and HBMEC/ciβ. Molecular Pharmaceutics 2019, 16 (5) , 2162-2171. https://doi.org/10.1021/acs.molpharmaceut.9b00114
  4. Huilong Luo, Elisa Rossi, Bruno Saubamea, Stéphanie Chasseigneaux, Véronique Cochois, Nina Choublier, Maria Smirnova, Fabienne Glacial, Nicolas Perrière, Sandrine Bourdoulous, David M. Smadja, Marie-Claude Menet, Pierre-Olivier Couraud, Salvatore Cisternino, Xavier Declèves. Cannabidiol Increases Proliferation, Migration, Tubulogenesis, and Integrity of Human Brain Endothelial Cells through TRPV2 Activation. Molecular Pharmaceutics 2019, 16 (3) , 1312-1326. https://doi.org/10.1021/acs.molpharmaceut.8b01252
  5. Kazuki Sato, Masanori Tachikawa, Michitoshi Watanabe, Eisuke Miyauchi, Yasuo Uchida, Tetsuya Terasaki. Identification of Blood–Brain Barrier-Permeable Proteins Derived from a Peripheral Organ: In Vivo and in Vitro Evidence of Blood-to-Brain Transport of Creatine Kinase. Molecular Pharmaceutics 2019, 16 (1) , 247-257. https://doi.org/10.1021/acs.molpharmaceut.8b00975
  6. Hiroki Kuroda, Masanori Tachikawa, Yuta Yagi, Mina Umetsu, Armania Nurdin, Eisuke Miyauchi, Michitoshi Watanabe, Yasuo Uchida, Tetsuya Terasaki. Cluster of Differentiation 46 Is the Major Receptor in Human Blood–Brain Barrier Endothelial Cells for Uptake of Exosomes Derived from Brain-Metastatic Melanoma Cells (SK-Mel-28). Molecular Pharmaceutics 2019, 16 (1) , 292-304. https://doi.org/10.1021/acs.molpharmaceut.8b00985
  7. Toshiki Kurosawa, Yuma Tega, Kei Higuchi, Tomoko Yamaguchi, Takashi Nakakura, Tatsuki Mochizuki, Hiroyuki Kusuhara, Kenji Kawabata, Yoshiharu Deguchi. Expression and Functional Characterization of Drug Transporters in Brain Microvascular Endothelial Cells Derived from Human Induced Pluripotent Stem Cells. Molecular Pharmaceutics 2018, 15 (12) , 5546-5555. https://doi.org/10.1021/acs.molpharmaceut.8b00697
  8. Huilong Luo, Matthieu Gauthier, Xi Tan, Christophe Landry, Joël Poupon, Marie-Pierre Dehouck, Fabien Gosselet, Nicolas Perrière, Frank Bellivier, Salvatore Cisternino, Xavier Declèves. Sodium Transporters Are Involved in Lithium Influx in Brain Endothelial Cells. Molecular Pharmaceutics 2018, 15 (7) , 2528-2538. https://doi.org/10.1021/acs.molpharmaceut.8b00018
  9. Zhengyu Zhang, Masanori Tachikawa, Yasuo Uchida, Tetsuya Terasaki. Drug Clearance from Cerebrospinal Fluid Mediated by Organic Anion Transporters 1 (Slc22a6) and 3 (Slc22a8) at Arachnoid Membrane of Rats. Molecular Pharmaceutics 2018, 15 (3) , 911-922. https://doi.org/10.1021/acs.molpharmaceut.7b00852
  10. Christine Wegler, Fabienne Z. Gaugaz, Tommy B. Andersson, Jacek R. Wiśniewski, Diana Busch, Christian Gröer, Stefan Oswald, Agneta Norén, Frederik Weiss, Helen S. Hammer, Thomas O. Joos, Oliver Poetz, Brahim Achour, Amin Rostami-Hodjegan, Evita van de Steeg, Heleen M. Wortelboer, and Per Artursson . Variability in Mass Spectrometry-based Quantification of Clinically Relevant Drug Transporters and Drug Metabolizing Enzymes. Molecular Pharmaceutics 2017, 14 (9) , 3142-3151. https://doi.org/10.1021/acs.molpharmaceut.7b00364
  11. Laura Pelkonen, Kazuki Sato, Mika Reinisalo, Heidi Kidron, Masanori Tachikawa, Michitoshi Watanabe, Yasuo Uchida, Arto Urtti, and Tetsuya Terasaki . LC–MS/MS Based Quantitation of ABC and SLC Transporter Proteins in Plasma Membranes of Cultured Primary Human Retinal Pigment Epithelium Cells and Immortalized ARPE19 Cell Line. Molecular Pharmaceutics 2017, 14 (3) , 605-613. https://doi.org/10.1021/acs.molpharmaceut.6b00782
  12. Paul A. Clark, Abraham J. Al-Ahmad, Tongcheng Qian, Ray R. Zhang, Hannah K. Wilson, Jamey P. Weichert, Sean P. Palecek, John S. Kuo, and Eric V. Shusta . Analysis of Cancer-Targeting Alkylphosphocholine Analogue Permeability Characteristics Using a Human Induced Pluripotent Stem Cell Blood–Brain Barrier Model. Molecular Pharmaceutics 2016, 13 (9) , 3341-3349. https://doi.org/10.1021/acs.molpharmaceut.6b00441
  13. Takanori Akazawa, Yasuo Uchida, Masanori Tachikawa, Sumio Ohtsuki, and Tetsuya Terasaki . Quantitative Targeted Absolute Proteomics of Transporters and Pharmacoproteomics-Based Reconstruction of P-Glycoprotein Function in Mouse Small Intestine. Molecular Pharmaceutics 2016, 13 (7) , 2443-2456. https://doi.org/10.1021/acs.molpharmaceut.6b00196
  14. Fei Liu, Michael Koval, Shoba Ranganathan, Susan Fanayan, William S. Hancock, Emma K. Lundberg, Ronald C. Beavis, Lydie Lane, Paula Duek, Leon McQuade, Neil L. Kelleher, and Mark S. Baker . Systems Proteomics View of the Endogenous Human Claudin Protein Family. Journal of Proteome Research 2016, 15 (2) , 339-359. https://doi.org/10.1021/acs.jproteome.5b00769
  15. Alice Gaudin, Oya Tagit, Dunja Sobot, Sinda Lepetre-Mouelhi, Julie Mougin, Thomas F. Martens, Kevin Braeckmans, Valérie Nicolas, Didier Desmaële, Stefaan C. de Smedt, Niko Hildebrandt, Patrick Couvreur, and Karine Andrieux . Transport Mechanisms of Squalenoyl-Adenosine Nanoparticles Across the Blood–Brain Barrier. Chemistry of Materials 2015, 27 (10) , 3636-3647. https://doi.org/10.1021/acs.chemmater.5b00267
  16. Anna Nilsson, Richard J. A. Goodwin, Mohammadreza Shariatgorji, Theodosia Vallianatou, Peter J. H. Webborn, and Per E. Andrén . Mass Spectrometry Imaging in Drug Development. Analytical Chemistry 2015, 87 (3) , 1437-1455. https://doi.org/10.1021/ac504734s
  17. Dake Qi, Haiyang Lin, Bingying Hu, Yang Wei. A review on in vitro model of the blood-brain barrier (BBB) based on hCMEC/D3 cells. Journal of Controlled Release 2023, 358 , 78-97. https://doi.org/10.1016/j.jconrel.2023.04.020
  18. Grace V. Aquino, Amjad Dabi, Gabriel J. Odom, Ramon Lavado, Kaitlin Nunn, Kathryn Thomas, Bennett Schackmuth, Nazeel Shariff, Manogna Jarajapu, Morgan Pluto, Sara R. Miller, Leah Eller, Justin Pressley, Rishi R. Patel, Jeffrey Black, Erica D. Bruce. Evaluating the Effect of Acute Diesel Exhaust Particle Exposure on P-glycoprotein Efflux Transporter in the Blood-Brain Barrier Co-cultured with Microglia. Current Research in Toxicology 2023, 102 , 100107. https://doi.org/10.1016/j.crtox.2023.100107
  19. Estrella Gonzales-Aloy, Aria Ahmed-Cox, Maria Tsoli, David S. Ziegler, Maria Kavallaris. From cells to organoids: The evolution of blood-brain barrier technology for modelling drug delivery in brain cancer. Advanced Drug Delivery Reviews 2023, 196 , 114777. https://doi.org/10.1016/j.addr.2023.114777
  20. David Gomez-Zepeda, Nicolas Perrière, Fabienne Glacial, Meryam Taghi, Cérina Chhuon, Jean-Michel Scherrmann, Philippe Sergent, Amélie Moreau, Claire Denizot, Yannick Parmentier, Salvatore Cisternino, Xavier Decleves, Marie-Claude Menet. Functional and targeted proteomics characterization of a human primary endothelial cell model of the blood-brain barrier (BBB) for drug permeability studies. Toxicology and Applied Pharmacology 2023, 465 , 116456. https://doi.org/10.1016/j.taap.2023.116456
  21. Kaoru Sato, Michiya Matsusaki. MPS for Blood Brain Barrier. YAKUGAKU ZASSHI 2023, 143 (1) , 45-53. https://doi.org/10.1248/yakushi.22-00161-2
  22. Li Di. Special issue on applications of in vitro, in vivo, and modeling and simulation tools for central nervous system drug disposition. Biopharmaceutics & Drug Disposition 2022, https://doi.org/10.1002/bdd.2342
  23. Nina Choublier, Meryam Taghi, Marie-Claude Menet, Morgane Le Gall, Johanna Bruce, Philippe Chafey, François Guillonneau, Amélie Moreau, Claire Denizot, Yannick Parmentier, Samir Nakib, Didier Borderie, Haniaa Bouzinba-Segard, Pierre-Olivier Couraud, Sandrine Bourdoulous, Xavier Declèves. Exposure of human cerebral microvascular endothelial cells hCMEC/D3 to laminar shear stress induces vascular protective responses. Fluids and Barriers of the CNS 2022, 19 (1) https://doi.org/10.1186/s12987-022-00344-w
  24. Marie-Pierre Dehouck, Masanori Tachikawa, Yutaro Hoshi, Kotaro Omori, Claude-Alain Maurage, Guillaume Strecker, Lucie Dehouck, Marie-Christine Boucau, Yasuo Uchida, Fabien Gosselet, Tetsuya Terasaki, Yannis Karamanos. Quantitative Targeted Absolute Proteomics for Better Characterization of an In Vitro Human Blood–Brain Barrier Model Derived from Hematopoietic Stem Cells. Cells 2022, 11 (24) , 3963. https://doi.org/10.3390/cells11243963
  25. Yu Sakurai, Himeka Watanabe, Kazuma Nishio, Kohei Hashimoto, Atsuki Harada, Masaki Gomi, Masayoshi Suzuki, Ryotaro Oyama, Takumi Handa, Risa Sato, Hina Takeuchi, Ryoga Taira, Kenta Tezuka, Kota Tange, Yuta Nakai, Hidetaka Akita, Yasuo Uchida. pH-Responsive Lipid Nanoparticles Achieve Efficient mRNA Transfection in Brain Capillary Endothelial Cells. Pharmaceutics 2022, 14 (8) , 1560. https://doi.org/10.3390/pharmaceutics14081560
  26. Kristiina M. Huttunen, Tetsuya Terasaki, Arto Urtti, Ahmed B. Montaser, Yasuo Uchida. Pharmacoproteomics of Brain Barrier Transporters and Substrate Design for the Brain Targeted Drug Delivery. Pharmaceutical Research 2022, 39 (7) , 1363-1392. https://doi.org/10.1007/s11095-022-03193-2
  27. Moeno Kadoguchi, Hiroshi Arakawa, Ryokichi Honda, Kazuki Hotta, Yoshiyuki Shirasaka, Yoshiharu Deguchi, Ikumi Tamai. Characterization of Aripiprazole Uptake Transporter in the Blood-Brain Barrier Model hCMEC/D3 Cells by Targeted siRNA Screening. Pharmaceutical Research 2022, 39 (7) , 1549-1559. https://doi.org/10.1007/s11095-022-03223-z
  28. Hinako Nagano, Shingo Ito, Takeshi Masuda, Sumio Ohtsuki. Effect of Insulin Receptor-Knockdown on the Expression Levels of Blood–Brain Barrier Functional Proteins in Human Brain Microvascular Endothelial Cells. Pharmaceutical Research 2022, 39 (7) , 1561-1574. https://doi.org/10.1007/s11095-021-03131-8
  29. Patrick T. Ronaldson, Thomas P. Davis. Transport Mechanisms at the Blood–Brain Barrier and in Cellular Compartments of the Neurovascular Unit: Focus on CNS Delivery of Small Molecule Drugs. Pharmaceutics 2022, 14 (7) , 1501. https://doi.org/10.3390/pharmaceutics14071501
  30. Deepak Ahire, Laken Kruger, Sheena Sharma, Vijaya Saradhi Mettu, Abdul Basit, Bhagwat Prasad, . Quantitative Proteomics in Translational Absorption, Distribution, Metabolism, and Excretion and Precision Medicine. Pharmacological Reviews 2022, 74 (3) , 771-798. https://doi.org/10.1124/pharmrev.121.000449
  31. Toshiki Kurosawa, Daiki Sako, Yuma Tega, Yasuyuki Debori, Yumi Tomihara, Kazunobu Aoyama, Yoshiyuki Kubo, Nobuyuki Amano, Yoshiharu Deguchi. Construction and Functional Evaluation of a Three-Dimensional Blood–Brain Barrier Model Equipped With Human Induced Pluripotent Stem Cell-Derived Brain Microvascular Endothelial Cells. Pharmaceutical Research 2022, 39 (7) , 1535-1547. https://doi.org/10.1007/s11095-022-03249-3
  32. William M. Pardridge. A Historical Review of Brain Drug Delivery. Pharmaceutics 2022, 14 (6) , 1283. https://doi.org/10.3390/pharmaceutics14061283
  33. Hinako Nagano, Seiryo Ogata, Shingo Ito, Takeshi Masuda, Sumio Ohtsuki. Knockdown of Podocalyxin Post-Transcriptionally Induces the Expression and Activity of ABCB1/MDR1 in Human Brain Microvascular Endothelial Cells. Journal of Pharmaceutical Sciences 2022, 111 (6) , 1812-1819. https://doi.org/10.1016/j.xphs.2022.02.006
  34. Lushan Wang, Timothy S. Wiedmann, Karunya K. Kandimalla. Modulating insulin signaling and trafficking at the blood-brain barrier endothelium using lipid based nanoemulsions. International Journal of Pharmaceutics 2022, 622 , 121823. https://doi.org/10.1016/j.ijpharm.2022.121823
  35. Vishal Sangha, Erica I. Williams, Patrick T. Ronaldson, Reina Bendayan. DRUG TRANSPORT IN THE BRAIN. 2022, 283-317. https://doi.org/10.1002/9781119739883.ch14
  36. Viktor Balzer, Pascal Poc, Elena Puris, Stefan Martin, Maryam Aliasgari, Seppo Auriola, Gert Fricker. Re-evaluation of the hCMEC/D3 based in vitro BBB model for ABC transporter studies. European Journal of Pharmaceutics and Biopharmaceutics 2022, 173 , 12-21. https://doi.org/10.1016/j.ejpb.2022.02.017
  37. Kelsy L. Nilles, Erica I. Williams, Robert D. Betterton, Thomas P. Davis, Patrick T. Ronaldson. Blood–Brain Barrier Transporters: Opportunities for Therapeutic Development in Ischemic Stroke. International Journal of Molecular Sciences 2022, 23 (3) , 1898. https://doi.org/10.3390/ijms23031898
  38. Takahiro Ishimoto, Yukio Kato. Ergothioneine in the brain. FEBS Letters 2022, 48 https://doi.org/10.1002/1873-3468.14271
  39. Dirk Gründemann, Lea Hartmann, Svenja Flögel. The ergothioneine transporter (ETT): substrates and locations, an inventory. FEBS Letters 2022, 62 https://doi.org/10.1002/1873-3468.14269
  40. Mehdi Taslimifar, Martin Faltys, Vartan Kurtcuoglu, François Verrey, Victoria Makrides. Analysis of L-leucine amino acid transporter species activity and gene expression by human blood brain barrier hCMEC/D3 model reveal potential LAT1, LAT4, B 0 AT2 and y + LAT1 functional cooperation. Journal of Cerebral Blood Flow & Metabolism 2022, 42 (1) , 90-103. https://doi.org/10.1177/0271678X211039593
  41. Shingo Ito, Takeshi Masuda, Sumio Ohtsuki. Quantitative and Targeted Proteomics of the Blood-Brain Barrier: Species and Cell Line Differences. 2022, 123-139. https://doi.org/10.1007/978-3-030-88773-5_5
  42. Hussein Akel, Ildikó Csóka, Rita Ambrus, Alexandra Bocsik, Ilona Gróf, Mária Mészáros, Anikó Szecskó, Gábor Kozma, Szilvia Veszelka, Mária A. Deli, Zoltán Kónya, Gábor Katona. In Vitro Comparative Study of Solid Lipid and PLGA Nanoparticles Designed to Facilitate Nose-to-Brain Delivery of Insulin. International Journal of Molecular Sciences 2021, 22 (24) , 13258. https://doi.org/10.3390/ijms222413258
  43. Kei Higuchi, Sathish Sivaprakasam, Souad R. Sennoune, Jiro Ogura, Yangzom D. Bhutia, Ricardo Rueda, Suzette L. Pereira, Vadivel Ganapathy. A Proton-Coupled Transport System for β-Hydroxy-β-Methylbutyrate (HMB) in Blood–Brain Barrier Endothelial Cell Line hCMEC/D3. Nutrients 2021, 13 (9) , 3220. https://doi.org/10.3390/nu13093220
  44. Leah A. Marquez-Curtis, Reid Bokenfohr, Locksley E. McGann, Janet A. W. Elliott, . Cryopreservation of human cerebral microvascular endothelial cells and astrocytes in suspension and monolayers. PLOS ONE 2021, 16 (4) , e0249814. https://doi.org/10.1371/journal.pone.0249814
  45. Guinever Eustaquio Do Imperio, Phetcharawan Lye, Enrrico Bloise, Stephen G. Matthews. Function of Multidrug Resistance Transporters is Disrupted by Infection Mimics in Human Brain Endothelial Cells. Tissue Barriers 2021, 9 (2) , 1860616. https://doi.org/10.1080/21688370.2020.1860616
  46. Yasuo Uchida. Quantitative Proteomics-Based Blood–Brain Barrier Study. Biological and Pharmaceutical Bulletin 2021, 44 (4) , 465-473. https://doi.org/10.1248/bpb.b21-00001
  47. Tetsuya Terasaki. Development of Novel Methodology and Its Application for Clarifying the Transport Function of the Blood-brain Barrier. YAKUGAKU ZASSHI 2021, 141 (4) , 447-462. https://doi.org/10.1248/yakushi.20-00232
  48. Laurens F. M. Verscheijden, Carlijn H. C. Litjens, Jan B. Koenderink, Ron H. J. Mathijssen, Marcel M. Verbeek, Saskia N. de Wildt, Frans G. M. Russel, . Physiologically based pharmacokinetic/pharmacodynamic model for the prediction of morphine brain disposition and analgesia in adults and children. PLOS Computational Biology 2021, 17 (3) , e1008786. https://doi.org/10.1371/journal.pcbi.1008786
  49. Takeshi Masuda, Ayano Mori, Shingo Ito, Sumio Ohtsuki. Quantitative and targeted proteomics-based identification and validation of drug efficacy biomarkers. Drug Metabolism and Pharmacokinetics 2021, 36 , 100361. https://doi.org/10.1016/j.dmpk.2020.09.006
  50. Patrick T. Ronaldson, Hrvoje Brzica, Wazir Abdullahi, Bianca G. Reilly, Thomas P. Davis. Transport Properties of Statins by Organic Anion Transporting Polypeptide 1A2 and Regulation by Transforming Growth Factor- β Signaling in Human Endothelial Cells. Journal of Pharmacology and Experimental Therapeutics 2021, 376 (2) , 148-160. https://doi.org/10.1124/jpet.120.000267
  51. Kandarp M. Dave, Wanzhu Zhao, Catherine Hoover, Anisha D’Souza, Devika S Manickam. Extracellular Vesicles Derived from a Human Brain Endothelial Cell Line Increase Cellular ATP Levels. AAPS PharmSciTech 2021, 22 (1) https://doi.org/10.1208/s12249-020-01892-w
  52. Ryoma Yokoyama, Toru Taharabaru, Takumi Nishida, Yoshitaka Ohno, Yuki Maeda, Masahiro Sato, Kandai Ishikura, Kazunori Yanagihara, Hiroki Takagi, Teruya Nakamura, Shingo Ito, Sumio Ohtsuki, Hidetoshi Arima, Risako Onodera, Taishi Higashi, Keiichi Motoyama. Lactose-appended β-cyclodextrin as an effective nanocarrier for brain delivery. Journal of Controlled Release 2020, 328 , 722-735. https://doi.org/10.1016/j.jconrel.2020.09.043
  53. Anna Gerhartl, Nadja Pracser, Alexandra Vladetic, Sabrina Hendrikx, Heinz-Peter Friedl, Winfried Neuhaus. The pivotal role of micro-environmental cells in a human blood–brain barrier in vitro model of cerebral ischemia: functional and transcriptomic analysis. Fluids and Barriers of the CNS 2020, 17 (1) https://doi.org/10.1186/s12987-020-00179-3
  54. Birthe Gericke, Kerstin Römermann, Andreas Noack, Sandra Noack, Jessica Kronenberg, Ingolf Ernst Blasig, Wolfgang Löscher. A face-to-face comparison of claudin-5 transduced human brain endothelial (hCMEC/D3) cells with porcine brain endothelial cells as blood–brain barrier models for drug transport studies. Fluids and Barriers of the CNS 2020, 17 (1) https://doi.org/10.1186/s12987-020-00212-5
  55. Young-Sun Lee, Ji-Young Choi, Sakulrat Mankhong, Sohee Moon, Sujin Kim, Young Ho Koh, Ji-Hye Kim, Ju-Hee Kang. Sirtuin 1-dependent regulation of high mobility box 1 in hypoxia–reoxygenated brain microvascular endothelial cells: roles in neuronal amyloidogenesis. Cell Death & Disease 2020, 11 (12) https://doi.org/10.1038/s41419-020-03293-0
  56. Lanxin Qiao, Yu Qin, Yaxin Wang, Yi Liang, Dunwan Zhu, Wei Xiong, Lu Li, Di Bao, Linhua Zhang, Xu Jin. A brain glioma gene delivery strategy by angiopep-2 and TAT-modified magnetic lipid-polymer hybrid nanoparticles. RSC Advances 2020, 10 (68) , 41471-41481. https://doi.org/10.1039/D0RA07161G
  57. Julia Tschirka, Markus Bach, Ilmars Kisis, Julia Lemmen, Mark Jean Gnoth, Dirk Gründemann. Transporter tandems: precise tools for normalizing active transporter in the plasma membrane. Biochemical Journal 2020, 477 (21) , 4191-4206. https://doi.org/10.1042/BCJ20200666
  58. Huilong Luo, Bruno Saubamea, Stéphanie Chasseigneaux, Véronique Cochois, Maria Smirnova, Fabienne Glacial, Nicolas Perrière, Catarina Chaves, Salvatore Cisternino, Xavier Declèves. Molecular and Functional Study of Transient Receptor Potential Vanilloid 1-4 at the Rat and Human Blood–Brain Barrier Reveals Interspecies Differences. Frontiers in Cell and Developmental Biology 2020, 8 https://doi.org/10.3389/fcell.2020.578514
  59. Solène Marie, Nicolas Tournier. Imagerie TEP pour l’étude des répercussions fonctionnelles de la P-glycoprotéine en neuropharmacocinétique. Therapies 2020, 75 (6) , 623-632. https://doi.org/10.1016/j.therap.2020.02.018
  60. A. Wünsch, D. Mulac, K. Langer. Lipoprotein imitating nanoparticles: Lecithin coating binds ApoE and mediates non-lysosomal uptake leading to transcytosis over the blood-brain barrier. International Journal of Pharmaceutics 2020, 589 , 119821. https://doi.org/10.1016/j.ijpharm.2020.119821
  61. Catarina Chaves, Tuan-Minh Do, Céline Cegarra, Valérie Roudières, Sandrine Tolou, Gilbert Thill, Corinne Rocher, Michel Didier, Dominique Lesuisse. Non-Human Primate Blood–Brain Barrier and In Vitro Brain Endothelium: From Transcriptome to the Establishment of a New Model. Pharmaceutics 2020, 12 (10) , 967. https://doi.org/10.3390/pharmaceutics12100967
  62. L. F. M. Verscheijden, A. C. van Hattem, J. C. L. M. Pertijs, C. A. de Jongh, R. M. Verdijk, B. Smeets, J. B. Koenderink, F. G. M. Russel, S. N. de Wildt. Developmental patterns in human blood–brain barrier and blood–cerebrospinal fluid barrier ABC drug transporter expression. Histochemistry and Cell Biology 2020, 154 (3) , 265-273. https://doi.org/10.1007/s00418-020-01884-8
  63. Yutaro Hoshi, Yasuo Uchida, Takashi Kuroda, Masanori Tachikawa, Pierre-Olivier Couraud, Takashi Suzuki, Tetsuya Terasaki. Distinct roles of ezrin, radixin and moesin in maintaining the plasma membrane localizations and functions of human blood–brain barrier transporters. Journal of Cerebral Blood Flow & Metabolism 2020, 40 (7) , 1533-1545. https://doi.org/10.1177/0271678X19868880
  64. Brahim Achour, Zubida M. Al-Majdoub, Amin Rostami-Hodjegan, Jill Barber. Mass Spectrometry of Human Transporters. Annual Review of Analytical Chemistry 2020, 13 (1) , 223-247. https://doi.org/10.1146/annurev-anchem-091719-024553
  65. Jiapeng Li, Hao-Jie Zhu. Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS)-Based Proteomics of Drug-Metabolizing Enzymes and Transporters. Molecules 2020, 25 (11) , 2718. https://doi.org/10.3390/molecules25112718
  66. Shingo Ito, Mariko Oishi, Seiryo Ogata, Tatsuki Uemura, Pierre-Olivier Couraud, Takeshi Masuda, Sumio Ohtsuki. Identification of Cell-Surface Proteins Endocytosed by Human Brain Microvascular Endothelial Cells In Vitro. Pharmaceutics 2020, 12 (6) , 579. https://doi.org/10.3390/pharmaceutics12060579
  67. Shunsuke Yamaguchi, Shingo Ito, Takeshi Masuda, Pierre-Olivier Couraud, Sumio Ohtsuki. Novel cyclic peptides facilitating transcellular blood-brain barrier transport of macromolecules in vitro and in vivo. Journal of Controlled Release 2020, 321 , 744-755. https://doi.org/10.1016/j.jconrel.2020.03.001
  68. Jiaojiao Cong, Yiling Ruan, Qinglin Lyu, Xiaohui Qin, Xinming Qi, Wenyuan Liu, Lifeng Kang, Junying Zhang, Chunyong Wu. A proton-coupled organic cation antiporter is involved in the blood-brain barrier transport of Aconitum alkaloids. Journal of Ethnopharmacology 2020, 252 , 112581. https://doi.org/10.1016/j.jep.2020.112581
  69. Masanori Tachikawa, Ryo Akaogi, Ayaka Taii, Shin-ichi Akanuma, Yasuo Uchida, Tetsuya Terasaki. Distinct Transport Properties of Human Pannexin 1 and Connexin 32 Hemichannels. Journal of Pharmaceutical Sciences 2020, 109 (3) , 1395-1402. https://doi.org/10.1016/j.xphs.2019.12.008
  70. E. Jacqueroux, S. Hodin, S. Saib, Z. He, V. Bin, O. Delézay, X. Delavenne. Value of quantifying ABC transporters by mass spectrometry and impact on in vitro-to-in vivo prediction of transporter-mediated drug-drug interactions of rivaroxaban. European Journal of Pharmaceutics and Biopharmaceutics 2020, 148 , 27-37. https://doi.org/10.1016/j.ejpb.2020.01.002
  71. Masanori Tachikawa, Yosuke Kaneko, Sumio Ohtsuki, Yasuo Uchida, Michitoshi Watanabe, Hideo Ohtsuka, Tetsuya Terasaki. Targeted Proteomics-Based Quantitative Protein Atlas of Pannexin and Connexin Subtypes in Mouse and Human Tissues and Cancer Cell Lines. Journal of Pharmaceutical Sciences 2020, 109 (2) , 1161-1168. https://doi.org/10.1016/j.xphs.2019.09.024
  72. Yasuo Uchida, Ryohei Goto, Hina Takeuchi, Magdalena Łuczak, Takuya Usui, Masanori Tachikawa, Tetsuya Terasaki. Abundant Expression of OCT2, MATE1, OAT1, OAT3, PEPT2, BCRP, MDR1, and xCT Transporters in Blood-Arachnoid Barrier of Pig and Polarized Localizations at CSF- and Blood-Facing Plasma Membranes. Drug Metabolism and Disposition 2020, 48 (2) , 135-145. https://doi.org/10.1124/dmd.119.089516
  73. Yutaro Hoshi, Yasuo Uchida, Masanori Tachikawa, Sumio Ohtsuki, Pierre-Olivier Couraud, Takashi Suzuki, Tetsuya Terasaki. Oxidative stress-induced activation of Abl and Src kinases rapidly induces P-glycoprotein internalization via phosphorylation of caveolin-1 on tyrosine-14, decreasing cortisol efflux at the blood–brain barrier. Journal of Cerebral Blood Flow & Metabolism 2020, 40 (2) , 420-436. https://doi.org/10.1177/0271678X18822801
  74. Jin-Ha Choi, Mallesh Santhosh, Jeong-Woo Choi. In Vitro Blood–Brain Barrier-Integrated Neurological Disorder Models Using a Microfluidic Device. Micromachines 2020, 11 (1) , 21. https://doi.org/10.3390/mi11010021
  75. David Gomez-Zepeda, Méryam Taghi, Jean-Michel Scherrmann, Xavier Decleves, Marie-Claude Menet. ABC Transporters at the Blood–Brain Interfaces, Their Study Models, and Drug Delivery Implications in Gliomas. Pharmaceutics 2020, 12 (1) , 20. https://doi.org/10.3390/pharmaceutics12010020
  76. Laura Hellinen, Kazuki Sato, Mika Reinisalo, Heidi Kidron, Kirsi Rilla, Masanori Tachikawa, Yasuo Uchida, Tetsuya Terasaki, Arto Urtti. Quantitative Protein Expression in the Human Retinal Pigment Epithelium: Comparison Between Apical and Basolateral Plasma Membranes With Emphasis on Transporters. Investigative Opthalmology & Visual Science 2019, 60 (15) , 5022. https://doi.org/10.1167/iovs.19-27328
  77. Tomohiro Nishimura, Yuichiro Sano, Yu Takahashi, Saki Noguchi, Yasuo Uchida, Akinori Takagi, Takahiro Tanaka, Satomi Katakura, Emi Nakashima, Masanori Tachikawa, Tetsuo Maruyama, Tetsuya Terasaki, Masatoshi Tomi. Quantification of ENT1 and ENT2 Proteins at the Placental Barrier and Contribution of These Transporters to Ribavirin Uptake. Journal of Pharmaceutical Sciences 2019, 108 (12) , 3917-3922. https://doi.org/10.1016/j.xphs.2019.09.005
  78. Gayathri Nair Sekhar, Alice L. Fleckney, Sevda Tomova Boyanova, Huzefa Rupawala, Rachel Lo, Hao Wang, Doaa B. Farag, Khondaker Miraz Rahman, Martin Broadstock, Suzanne Reeves, Sarah Ann Thomas. Region-specific blood–brain barrier transporter changes leads to increased sensitivity to amisulpride in Alzheimer’s disease. Fluids and Barriers of the CNS 2019, 16 (1) https://doi.org/10.1186/s12987-019-0158-1
  79. Xiaofen Zhao, Yangfang Li, Kun Du, Yuqin Wu, Ling Liu, Shan Cui, Yan Zhang, Jin Gao, Richard F. Keep, Jianming Xiang, . Involvement of human and canine MRP1 and MRP4 in benzylpenicillin transport. PLOS ONE 2019, 14 (11) , e0225702. https://doi.org/10.1371/journal.pone.0225702
  80. Xiao-wei Ding, Xia Sun, Xue-fang Shen, Yan Lu, Jia-qiang Wang, Zhi-rong Sun, Chang-hong Miao, Jia-wei Chen. Propofol attenuates TNF-α-induced MMP-9 expression in human cerebral microvascular endothelial cells by inhibiting Ca2+/CAMK II/ERK/NF-κB signaling pathway. Acta Pharmacologica Sinica 2019, 40 (10) , 1303-1313. https://doi.org/10.1038/s41401-019-0258-0
  81. Lina Bergman, Pablo Torres-Vergara, Jeffrey Penny, Johan Wikström, Maria Nelander, Jose Leon, Mary Tolcher, James M. Roberts, Anna-Karin Wikström, Carlos Escudero. Investigating Maternal Brain Alterations in Preeclampsia: the Need for a Multidisciplinary Effort. Current Hypertension Reports 2019, 21 (9) https://doi.org/10.1007/s11906-019-0977-0
  82. Yusuke Ochiai, Yasuo Uchida, Masanori Tachikawa, Pierre‐Olivier Couraud, Tetsuya Terasaki. Amyloid beta 25‐35 impairs docosahexaenoic acid efflux by down‐regulating fatty acid transport protein 1 (FATP1/SLC27A1) protein expression in human brain capillary endothelial cells. Journal of Neurochemistry 2019, 150 (4) , 385-401. https://doi.org/10.1111/jnc.14722
  83. Liwen Deng, Brady L. Spencer, Joshua A. Holmes, Rong Mu, Sara Rego, Thomas A. Weston, Yoonsung Hu, Glenda F. Sanches, Sunghyun Yoon, Nogi Park, Prescilla E. Nagao, Howard F. Jenkinson, Justin A. Thornton, Keun Seok Seo, Angela H. Nobbs, Kelly S. Doran, . The Group B Streptococcal surface antigen I/II protein, BspC, interacts with host vimentin to promote adherence to brain endothelium and inflammation during the pathogenesis of meningitis. PLOS Pathogens 2019, 15 (6) , e1007848. https://doi.org/10.1371/journal.ppat.1007848
  84. Sulay H. Patel, Omnia A. Ismaiel, William R. Mylott, Moucun Yuan, Kurt F. Hauser, MaryPeace McRae. Simultaneous determination of intracellular concentrations of tenofovir, emtricitabine, and dolutegravir in human brain microvascular endothelial cells using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Analytica Chimica Acta 2019, 1056 , 79-87. https://doi.org/10.1016/j.aca.2019.01.015
  85. David Gomez-Zepeda, Meryam Taghi, Maria Smirnova, Philippe Sergent, Wang-Qing Liu, Cerina Chhuon, Michel Vidal, Martin Picard, Elizabeth Thioulouse, Isabelle Broutin, Ida-Chiara Guerrera, Jean-Michel Scherrmann, Yannick Parmentier, Xavier Decleves, Marie-Claude Menet. LC–MS/MS-based quantification of efflux transporter proteins at the BBB. Journal of Pharmaceutical and Biomedical Analysis 2019, 164 , 496-508. https://doi.org/10.1016/j.jpba.2018.11.013
  86. Keith D. Rochfort, Philip M. Cummins. In Vitro Cell Models of the Human Blood-Brain Barrier: Demonstrating the Beneficial Influence of Shear Stress on Brain Microvascular Endothelial Cell Phenotype. 2019, 71-98. https://doi.org/10.1007/978-1-4939-8946-1_5
  87. Yu Takahashi, Tomohiro Nishimura, Kei Higuchi, Saki Noguchi, Yuma Tega, Toshiki Kurosawa, Yoshiharu Deguchi, Masatoshi Tomi. Transport of Pregabalin Via L-Type Amino Acid Transporter 1 (SLC7A5) in Human Brain Capillary Endothelial Cell Line. Pharmaceutical Research 2018, 35 (12) https://doi.org/10.1007/s11095-018-2532-0
  88. Stephen B. Hladky, Margery A. Barrand. Elimination of substances from the brain parenchyma: efflux via perivascular pathways and via the blood–brain barrier. Fluids and Barriers of the CNS 2018, 15 (1) https://doi.org/10.1186/s12987-018-0113-6
  89. Junzhi Yang, Bianca Reilly, Thomas Davis, Patrick Ronaldson. Modulation of Opioid Transport at the Blood-Brain Barrier by Altered ATP-Binding Cassette (ABC) Transporter Expression and Activity. Pharmaceutics 2018, 10 (4) , 192. https://doi.org/10.3390/pharmaceutics10040192
  90. Yordenca Lamartinière, Marie-Christine Boucau, Lucie Dehouck, Markus Krohn, Jens Pahnke, Pietra Candela, Fabien Gosselet, Laurence Fenart. ABCA7 Downregulation Modifies Cellular Cholesterol Homeostasis and Decreases Amyloid-β Peptide Efflux in an in vitro Model of the Blood-Brain Barrier. Journal of Alzheimer's Disease 2018, 64 (4) , 1195-1211. https://doi.org/10.3233/JAD-170883
  91. Cynthia Hajal, Marco Campisi, Clara Mattu, Valeria Chiono, Roger D. Kamm. In vitro models of molecular and nano-particle transport across the blood-brain barrier. Biomicrofluidics 2018, 12 (4) , 042213. https://doi.org/10.1063/1.5027118
  92. Liwen Deng, Rong Mu, Thomas A. Weston, Brady L. Spencer, Roxanne P. Liles, Kelly S. Doran, . Characterization of a Two-Component System Transcriptional Regulator, LtdR, That Impacts Group B Streptococcal Colonization and Disease. Infection and Immunity 2018, 86 (7) https://doi.org/10.1128/IAI.00822-17
  93. Szilvia Veszelka, András Tóth, Fruzsina R. Walter, Andrea E. Tóth, Ilona Gróf, Mária Mészáros, Alexandra Bocsik, Éva Hellinger, Monika Vastag, Gábor Rákhely, Mária A. Deli. Comparison of a Rat Primary Cell-Based Blood-Brain Barrier Model With Epithelial and Brain Endothelial Cell Lines: Gene Expression and Drug Transport. Frontiers in Molecular Neuroscience 2018, 11 https://doi.org/10.3389/fnmol.2018.00166
  94. Isobel Parkes, Satyan Chintawar, M. Zameel Cader. Neurovascular dysfunction in dementia – human cellular models and molecular mechanisms. Clinical Science 2018, 132 (3) , 399-418. https://doi.org/10.1042/CS20160720
  95. Yi-Nan Zhang, Yan-Fang Yang, Xiu-Wei Yang. Blood-brain barrier permeability and neuroprotective effects of three main alkaloids from the fruits of Euodia rutaecarpa with MDCK-pHaMDR cell monolayer and PC12 cell line. Biomedicine & Pharmacotherapy 2018, 98 , 82-87. https://doi.org/10.1016/j.biopha.2017.12.017
  96. Yumi Yamamoto, Pyry A. Välitalo, Yin Cheong Wong, Dymphy R. Huntjens, Johannes H. Proost, An Vermeulen, Walter Krauwinkel, Margot W. Beukers, Hannu Kokki, Merja Kokki, Meindert Danhof, Johan G.C. van Hasselt, Elizabeth C.M. de Lange. Prediction of human CNS pharmacokinetics using a physiologically-based pharmacokinetic modeling approach. European Journal of Pharmaceutical Sciences 2018, 112 , 168-179. https://doi.org/10.1016/j.ejps.2017.11.011
  97. Kaoru Sato. Consideration for future in vitro BBB models — technical development to investigate the drug delivery to the CNS. Folia Pharmacologica Japonica 2018, 152 (6) , 287-294. https://doi.org/10.1254/fpj.152.287
  98. Mitchell P. McInerney, Yijun Pan, Jennifer L. Short, Joseph A. Nicolazzo. Development and Validation of an In-Cell Western for Quantifying P-Glycoprotein Expression in Human Brain Microvascular Endothelial (hCMEC/D3) Cells. Journal of Pharmaceutical Sciences 2017, 106 (9) , 2614-2624. https://doi.org/10.1016/j.xphs.2016.12.017
  99. Shingo Ito, Mari Yanai, Shunsuke Yamaguchi, Pierre-Olivier Couraud, Sumio Ohtsuki. Regulation of Tight-Junction Integrity by Insulin in an In Vitro Model of Human Blood–Brain Barrier. Journal of Pharmaceutical Sciences 2017, 106 (9) , 2599-2605. https://doi.org/10.1016/j.xphs.2017.04.036
  100. Marilyn E. Morris, Vivian Rodriguez-Cruz, Melanie A. Felmlee. SLC and ABC Transporters: Expression, Localization, and Species Differences at the Blood-Brain and the Blood-Cerebrospinal Fluid Barriers. The AAPS Journal 2017, 19 (5) , 1317-1331. https://doi.org/10.1208/s12248-017-0110-8
Load all citations

Pair your accounts.

Export articles to Mendeley

Get article recommendations from ACS based on references in your Mendeley library.

Pair your accounts.

Export articles to Mendeley

Get article recommendations from ACS based on references in your Mendeley library.

You’ve supercharged your research process with ACS and Mendeley!

STEP 1:
Click to create an ACS ID

Please note: If you switch to a different device, you may be asked to login again with only your ACS ID.

Please note: If you switch to a different device, you may be asked to login again with only your ACS ID.

Please note: If you switch to a different device, you may be asked to login again with only your ACS ID.

MENDELEY PAIRING EXPIRED
Your Mendeley pairing has expired. Please reconnect