title: Effect of Long-term In Vitro Lithium Exposure on mRNA Levels of Claudin-3, CYP1A1, ABCG2 and GSTM3 Genes in the hCMEC/D3 Human Brain Endothelial Cell Line.
abstract: OBJECTIVE
  Lithium chloride (LiCl) has been shown to improve the tightness of brain endothelial cell monolayers in vitro by inhibition of the GSK-3β enzyme, activation of the Wnt/beta-catenin pathway and regulation of tight junction (TJ) protein expression. However, the effect of LiCl on the drug transporters and drug-metabolizing enzymes has not been addressed so far. The hCMEC/D3 cell line is a validated in vitro BBB model expressing transporters and drug-metabolizing enzymes (phase 1 and 2). The present study was conducted to compare the mRNAs levels corresponding to several BBB endothelial markers in hCMEC/D3 cells with and without incubation in LiCl.
  
  
  METHODS
  We used quantitative real-time polymerase chain reaction (qRT-PCR) to quantify the mRNA expression of 5 tight junction (TJ) proteins, 4 adhesion proteins, 5 solute carriers, 7 ATP-binding cassette (ABC) transporters, 8 cytochrome P450 (CYP) and 17 phase 2 conjugation enzymes in hCMEC/D3 cells with and without incubation in LiCl.
  
  
  RESULTS
  Our study showed that LiCl treatment for 6 days at a concentration of 10 mM induced the TJ protein claudin-3, the ABC transporter BCRP/ABCG2, the cytochrome P-450 CYP1A1 and the glutathione-S-transferase GSTM3, while the other selected markers were not significantly affected.
  
  
  CONCLUSIONS
  Our findings provide new insights into the effects of lithium on some drug transporters and drug-metabolizing enzymes in the BBB that may have consequences in pharmacotherapy.
authors.affiliation: Inserm, U1144, Paris, 75006, France.|Faculté de Pharmacie, Inserm UMR-S1144, Université Paris Descartes, 4 Avenue de L'observatoire, 75006, Paris, France.|Department of Physiology, Pharmacology, and Toxicology, Faculty of Medicine and Health Sciences, An-Najah National University, Nablus, Palestine.
authors.forename: Ramzi
authors.initials: R
authors.lastname: Shawahna
authors.affiliation: Inserm U1016, Institut Cochin, Paris, France.|CNRS, UMR 8104, Paris, France.|Université Paris Descartes Sorbonne Paris Cité, Paris, France.
authors.forename: Kayathiri
authors.initials: K
authors.lastname: Ganeshamoorthy
authors.affiliation: Inserm, U1144, Paris, 75006, France.|Faculté de Pharmacie, Inserm UMR-S1144, Université Paris Descartes, 4 Avenue de L'observatoire, 75006, Paris, France.
authors.forename: Luo
authors.initials: L
authors.lastname: Huilong
authors.affiliation: Inserm, U1144, Paris, 75006, France.|Faculté de Pharmacie, Inserm UMR-S1144, Université Paris Descartes, 4 Avenue de L'observatoire, 75006, Paris, France.
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Scherrmann
authors.affiliation: Inserm U1016, Institut Cochin, Paris, France.|CNRS, UMR 8104, Paris, France.|Université Paris Descartes Sorbonne Paris Cité, Paris, France.
authors.forename: Pierre-Olivier
authors.initials: PO
authors.lastname: Couraud
authors.affiliation: Inserm, U1144, Paris, 75006, France. xavier.decleves@parisdescartes.fr.|Faculté de Pharmacie, Inserm UMR-S1144, Université Paris Descartes, 4 Avenue de L'observatoire, 75006, Paris, France. xavier.decleves@parisdescartes.fr.
authors.forename: Xavier
authors.initials: X
authors.lastname: Declèves
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2 / Q000235:genetics*; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000166:cytology*; D002460:Cell Line; D062465:Claudin-3 / Q000235:genetics*; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics*; D042783:Endothelial Cells / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D018021:Lithium Chloride / Q000008:administration & dosage / Q000494:pharmacology*; D009363:Neoplasm Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*
chemical_list: C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D015415:Biomarkers; C568122:CLDN3 protein, human; D062465:Claudin-3; D009363:Neoplasm Proteins; D012333:RNA, Messenger; C569463:CYP1A1 protein, human; D019363:Cytochrome P-450 CYP1A1; C483009:GSTM3 protein, human; D005982:Glutathione Transferase; D018021:Lithium Chloride