Cilostazol attenuates ischemia-reperfusion-induced blood-brain barrier dysfunction enhanced by advanced glycation endproducts via transforming growth factor-ß1 signaling.
Mol Cell Neurosci
; 60: 1-9, 2014 May.
Article
em En
| MEDLINE
| ID: mdl-24472843
ABSTRACT
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)-ß1, cilostazol inhibited the production of extracellular TGF-ß1 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-ß1. Cilostazol appeared to limit ischemia-reperfusion injury with AGEs by improving the TJ proteins and inhibiting TGF-ß1 signaling.
Palavras-chave
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Tetrazóis
/
Barreira Hematoencefálica
/
Hipóxia Celular
/
Produtos Finais de Glicação Avançada
/
Pericitos
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Fator de Crescimento Transformador beta1
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Inibidores da Fosfodiesterase 3
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Mol Cell Neurosci
Assunto da revista:
BIOLOGIA MOLECULAR
/
NEUROLOGIA
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Japão