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Modulation of P-glycoprotein in rat brain microvessel endothelial cells under oxygen glucose deprivation.

Research paper by Bian-Sheng BS Ji, Juan J Cen, Ling L He, Meng M Liu, Yan-Qing YQ Liu, Lu L Liu

Indexed on: 14 Sep '13Published on: 14 Sep '13Published in: Journal of Pharmacy and Pharmacology



Abstract

To investigate modulation of P-glycoprotein (P-gp) in rat brain microvessel endothelial cells (rBMECs) under oxygen glucose deprivation (OGD).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.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.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.