rdf:type |
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lifeskim:mentions |
umls-concept:C0005854,
umls-concept:C0017262,
umls-concept:C0021467,
umls-concept:C0021469,
umls-concept:C0031164,
umls-concept:C0078058,
umls-concept:C0185117,
umls-concept:C0291979,
umls-concept:C0442805,
umls-concept:C0680242,
umls-concept:C0965644,
umls-concept:C1256770,
umls-concept:C1333897,
umls-concept:C1704838,
umls-concept:C2911684
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pubmed:issue |
2
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pubmed:dateCreated |
2007-7-26
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pubmed:abstractText |
Cerebral microvascular endothelial cells form the anatomical basis of the blood-brain barrier (BBB), and the tight junctions of the BBB are critical for maintaining brain homeostasis and low permeability. Ischemia/reperfusion is known to damage the tight junctions of BBB and lead to permeability changes. Here we investigated the protective role of 3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole (YC-1), against chemical hypoxia and hypoxia/reoxygenation (H/R)-induced BBB hyperpermeability using adult rat brain endothelial cell culture (ARBEC). YC-1 significantly decreased CoCl2- and H/R-induced hyperpermeability of fluorescein isothiocyanate (FITC)-dextran in cell culture inserts. It was found that the decrease and disorganization of tight junction protein zonular occludens-1 (ZO-1) in response to CoCl2, and H/R was antagonized by YC-1. The protection of YC-1 may result from the inhibition of HIF-1alpha accumulation and production of its downstream target vascular endothelial growth factor (VEGF). VEGF alone significantly increased FITC-dextran permeability and down-regulated mRNA and protein levels of ZO-1 in ARBECs. We further used animal model to examine the effect of YC-1 on BBB permeability after cerebral ischemia/reperfusion. It was found that YC-1 significantly protected the BBB against ischemia/reperfusion-induced injury. Taken together, these results indicate that YC-1 may inhibit HIF-1alpha accumulation and VEGF production, which in turn protect BBB from injury caused by hypoxia.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/3-(5'-hydroxymethyl-2'-furyl)-1-benz...,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic GMP,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic GMP-Dependent Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Hif1a protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Hypoxia-Inducible Factor 1, alpha...,
http://linkedlifedata.com/resource/pubmed/chemical/Indazoles,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Vascular Endothelial Growth Factor A,
http://linkedlifedata.com/resource/pubmed/chemical/zonula occludens-1 protein
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0026-895X
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pubmed:author |
|
pubmed:issnType |
Print
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pubmed:volume |
72
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
440-9
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:17513385-Animals,
pubmed-meshheading:17513385-Blood-Brain Barrier,
pubmed-meshheading:17513385-Cell Hypoxia,
pubmed-meshheading:17513385-Cells, Cultured,
pubmed-meshheading:17513385-Cyclic GMP,
pubmed-meshheading:17513385-Cyclic GMP-Dependent Protein Kinases,
pubmed-meshheading:17513385-Hypoxia-Inducible Factor 1, alpha Subunit,
pubmed-meshheading:17513385-Indazoles,
pubmed-meshheading:17513385-Ischemia,
pubmed-meshheading:17513385-Male,
pubmed-meshheading:17513385-Membrane Proteins,
pubmed-meshheading:17513385-Permeability,
pubmed-meshheading:17513385-Phosphoproteins,
pubmed-meshheading:17513385-Rats,
pubmed-meshheading:17513385-Rats, Sprague-Dawley,
pubmed-meshheading:17513385-Reperfusion Injury,
pubmed-meshheading:17513385-Vascular Endothelial Growth Factor A
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pubmed:year |
2007
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pubmed:articleTitle |
Inhibition of hypoxia-induced increase of blood-brain barrier permeability by YC-1 through the antagonism of HIF-1alpha accumulation and VEGF expression.
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pubmed:affiliation |
Department of pharmacology, College of Medicine, National Taiwan University, 1, Sec. 1, Jen-Ai Road, Taipei, Taiwan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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