Cilostazol attenuates ischemia?reperfusion-induced blood?brain barrier dysfunction enhanced by advanced glycation endproducts via transforming growth factor-β1 signaling
| Autor: | Gohei So, Izumi Nagata, Mária A. Deli, Tomonori Takeshita, Masami Niwa, Kentaro Hayashi, Rie Tatsumi, Shinsuke Nakagawa, Kunihiko Tanaka |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Glycation End Products
Advanced medicine.medical_specialty Phosphodiesterase 3 Ischemia Tetrazoles Biology Blood–brain barrier Phosphodiesterase 3 Inhibitors Tight Junctions Capillary Permeability Transforming Growth Factor beta1 Cellular and Molecular Neuroscience Western blot Internal medicine medicine Extracellular Electric Impedance Animals Claudin-5 Rats Wistar Molecular Biology Cells Cultured Blood-brain barrier medicine.diagnostic_test Tight junction Advanced glycation endproducts Transforming growth factor-β Cell Biology medicine.disease Cell Hypoxia Oxygen glucose deprivation/reoxygenation Cilostazol Rats Endocrinology medicine.anatomical_structure Astrocytes Reperfusion Injury Pericytes Transforming growth factor medicine.drug Signal Transduction |
| Zdroj: | Molecular and Cellular Neuroscience. 60:1-9 |
| ISSN: | 1044-7431 |
| Popis: | We investigated the effects of cilostazol, a selective inhibitor of phosphodiesterase 3, on blood-brain barrier (BBB) integrity against ischemia-reperfusion injury enhanced by advanced glycation endproducts (AGEs). We used in vitro BBB models with primarily cultured BBB-related cells from rats (brain capillary endothelial cells, astrocytes and pericytes), and subjected cells to either normoxia or 3-h oxygen glucose deprivation (OGD)/24-h reoxygenation with or without AGEs. Treatment of AGEs did not affect the transendothelial electrical resistance (TEER) in the BBB model under normoxia, but there was a significant decrease in TEER under 3-h OGD/24-h reoxygenation conditions with AGEs. Cilostazol inhibited decreases in TEER induced by 3-h OGD/24-h reoxygenation with AGEs. Immunocytochemical and Western blot analyses showed that AGEs reduced the expression of claudin-5, the main functional protein of tight junctions (TJs). In contrast, cilostazol increased the expression of claudin-5 under 3-h OGD/24-h reoxygenation with AGEs. Furthermore, while AGEs increased the production of extracellular transforming growth factor (TGF)-β1, cilostazol inhibited the production of extracellular TGF-β1 and restored the integrity of TJs. Thus, we found that AGEs enhanced ischemia-reperfusion injury, which mainly included decreases in the expression of proteins comprising TJs through the production of TGF-β1. Cilostazol appeared to limit ischemia-reperfusion injury with AGEs by improving the TJ proteins and inhibiting TGF-β1 signaling. Molecular and Cellular Neuroscience, 60, pp.1-9; 2014 |
| Databáze: | OpenAIRE |
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