HMGB1 promoted P-glycoprotein at the blood-brain barrier in MCAO rats via TLR4/NF-κB signaling pathway
| Autor: | Bian-Sheng Ji, Lu Liu, Fei Wang, Muxi Wang, Fuxia Jiang, Shenglan Ji, Qiaoling Li, Juan Cen |
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| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine TIRAP Ischemia Pharmacology Blood–brain barrier HMGB1 Rats Sprague-Dawley 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Downregulation and upregulation Pyrrolidine dithiocarbamate medicine Animals ATP Binding Cassette Transporter Subfamily B Member 1 HMGB1 Protein Microvessel Cells Cultured biology Chemistry NF-kappa B Endothelial Cells Infarction Middle Cerebral Artery medicine.disease Coculture Techniques Toll-Like Receptor 4 030104 developmental biology medicine.anatomical_structure Blood-Brain Barrier Astrocytes biology.protein Signal transduction 030217 neurology & neurosurgery Signal Transduction |
| Zdroj: | European Journal of Pharmacology. 880:173189 |
| ISSN: | 0014-2999 |
| Popis: | P-glycoprotein (P-gp) is located on the luminal surface of brain vascular endothelium and its status may determine the delivery of the agents into the brain tissues. Previous study showed that upregulation of P-gp at the blood-brain barrier (BBB) after ischemic stroke were mediated by nuclear factor-B (NF-kB) and tumour necrosis factor-α (TNF-α). Based on middle cerebral artery occlusion (MCAO) rats and oxygen-glucose deprivation (OGD) in co-culture of rat brain microvessel endothelial cells (rBMECs) and astrocytes system, the present data indicated that potentiated P-gp expression and activity in brain microvessels or rBMECs were associated with the increase in high-mobility group box 1 (HMGB1), Toll-like receptor 4 (TLR4) and activation of NF-kB and that HMGB1 can release from nucleus to the cytoplasm in activated astrocytes, then into the medium. Moreover, changes in TLR4, TIR domain-containing adaptor protein (TIRAP), NF-kB and P-gp in rBMECs were attenuated by addition of 1 mM ethyl pyruvate (EP), 10 μM TAK-242 and 10 μM pyrrolidine dithiocarbamate (PDTC), respectively. These results demonstrated that HMGB1 promoted P-gp at the BBB after cerebral ischemia via TLR4/NF-κB signaling pathway. |
| Databáze: | OpenAIRE |
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