title: Modulation of P-glycoprotein in rat brain microvessel endothelial cells under oxygen glucose deprivation.
abstract: OBJECTIVE
  To investigate modulation of P-glycoprotein (P-gp) in rat brain microvessel endothelial cells (rBMECs) under oxygen glucose deprivation (OGD).
  
  
  METHODS
  The coculture of rBMECs and astrocytes was established to investigate the time course of P-gp, tumour necrosis factor-α (TNF-α), endothelin-1 (ET-1), nitric oxide synthase (NOS) and protein kinase C (PKC) expression in the rBMECs as well as rhodamine 123 (Rh123) transendothelial transfer under OGD using Western blot and HPLC, respectively. The influence of pharmacological tools including H398, JKC-301, RES-701-1, L-NMMA, BIM and SN50 on the P-gp expression as well as Rh123 transendothelial transfer was evaluated at 3 h time point of OGD.
  
  
  RESULTS
  Elevated P-gp, TNF-α, ET-1, NOS and PKC expression in the rBMECs, as well as increased P-gp efflux activity were observed after 2 h or more time of OGD. Incubation of H398 and other pharmacological tools downregulated P-gp expression and functional activity in the rBMECs at 3 h time point of OGD.
  
  
  CONCLUSIONS
  This report suggested that TNF-α, ET-1, NOS and PKC may mediate upregulation of P-gp in the rBMECs under OGD, which may be worthy of being referenced for the investigation of P-gp at the blood-brain barrier in the early period of stroke.
authors.affiliation: Key Laboratory of Natural Medicine and Immune Engineering, Henan University, Kaifeng, China.
authors.forename: Bian-Sheng
authors.initials: BS
authors.lastname: Ji
authors.forename: Juan
authors.initials: J
authors.lastname: Cen
authors.forename: Ling
authors.initials: L
authors.lastname: He
authors.forename: Meng
authors.initials: M
authors.lastname: Liu
authors.forename: Yan-Qing
authors.initials: YQ
authors.lastname: Liu
authors.forename: Lu
authors.initials: L
authors.lastname: Liu
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism; D015153:Blotting, Western; D001921:Brain / Q000098:blood supply* / Q000378:metabolism; D015687:Cell Hypoxia; D002470:Cell Survival; D002851:Chromatography, High Pressure Liquid; D018920:Coculture Techniques; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D055806:Microvessels / Q000166:cytology / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism*; D061251:Primary Cell Culture; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D005947:Glucose; D010100:Oxygen
keywords: P-glycoprotein; oxygen glucose deprivation; rat brain microvessel endothelial cells; transendothelial transfer