File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Caveolin-1 regulates nitric oxide-mediated matrix metalloproteinases activity and blood-brain barrier permeability in focal cerebral ischemia and reperfusion injury

TitleCaveolin-1 regulates nitric oxide-mediated matrix metalloproteinases activity and blood-brain barrier permeability in focal cerebral ischemia and reperfusion injury
Authors
Keywordsblood-brain barrier
caveolin-1
ischemia
nitric oxide synthase
Issue Date2012
PublisherBlackwell Publishing Ltd.
Citation
Journal Of Neurochemistry, 2012, v. 120 n. 1, p. 147-156 How to Cite?
AbstractThe roles of caveolin-1 (cav-1) in regulating blood-brain barrier (BBB) permeability are unclear yet. We previously reported that cav-1 was down-regulated and the production of nitric oxide (NO) induced the loss of cav-1 in focal cerebral ischemia and reperfusion injury. The present study aims to address whether the loss of cav-1 impacts on BBB permeability and matrix metalloproteinases (MMPs) activity during cerebral ischemia-reperfusion injury. We found that focal cerebral ischemia-reperfusion down-regulated the expression of cav-1 in isolated cortex microvessels, hippocampus, and cortex of ischemic brain. The down-regulation of cav-1 was correlated with the increased MMP-2 and -9 activities, decreased tight junction (TJ) protein zonula occludens (ZO)-1 expression and enhanced BBB permeability. Treatment of N G-nitro-l- arginine methyl ester [l-NAME, a non-selective nitric oxide synthase (NOS) inhibitor] reserved the expression of cav-1, inhibited MMPs activity, and reduced BBB permeability. To elucidate the roles of cav-1 in regulating MMPs and BBB permeability, we used two approaches including cav-1 knockdown in cultured brain microvascular endothelial cells (BMECs) in vitro and cav-1 knockout (KO) mice in vivo. Cav-1 knockdown remarkably increased MMPs activity in BMECs. Meanwhile, with focal cerebral ischemia-reperfusion, cav-1 deficiency mice displayed higher MMPs activities and BBB permeability than wild-type mice. Interestingly, the effects of l-NAME on MMPs activity and BBB permeability was partly reversed in cav-1 deficiency mice. These results, when taken together, suggest that cav-1 plays important roles in regulating MMPs activity and BBB permeability in focal cerebral ischemia and reperfusion injury. The effects of l-NAME on MMPs activity and BBB permeability are partly mediated by preservation of cav-1. © 2011 International Society for Neurochemistry.
Persistent Identifierhttp://hdl.handle.net/10722/146635
ISSN
2015 Impact Factor: 3.842
2015 SCImago Journal Rankings: 2.021
ISI Accession Number ID
Funding AgencyGrant Number
University Grants Committee774408M
777611M
Hong Kong Special Administration Region
University of Hong Kong
Funding Information:

This study was mainly supported by General Research Fund from University Grants Committee (774408M, 777611M), Hong Kong Special Administration Region and Seed fund for Basic Research from The University of Hong Kong.

References

 

DC FieldValueLanguage
dc.contributor.authorGu, Yen_HK
dc.contributor.authorZheng, Gen_HK
dc.contributor.authorXu, Men_HK
dc.contributor.authorLi, Yen_HK
dc.contributor.authorChen, Xen_HK
dc.contributor.authorZhu, Wen_HK
dc.contributor.authorTong, Yen_HK
dc.contributor.authorChung, SKen_HK
dc.contributor.authorLiu, KJen_HK
dc.contributor.authorShen, Jen_HK
dc.date.accessioned2012-05-08T03:21:25Z-
dc.date.available2012-05-08T03:21:25Z-
dc.date.issued2012en_HK
dc.identifier.citationJournal Of Neurochemistry, 2012, v. 120 n. 1, p. 147-156en_HK
dc.identifier.issn0022-3042en_HK
dc.identifier.urihttp://hdl.handle.net/10722/146635-
dc.description.abstractThe roles of caveolin-1 (cav-1) in regulating blood-brain barrier (BBB) permeability are unclear yet. We previously reported that cav-1 was down-regulated and the production of nitric oxide (NO) induced the loss of cav-1 in focal cerebral ischemia and reperfusion injury. The present study aims to address whether the loss of cav-1 impacts on BBB permeability and matrix metalloproteinases (MMPs) activity during cerebral ischemia-reperfusion injury. We found that focal cerebral ischemia-reperfusion down-regulated the expression of cav-1 in isolated cortex microvessels, hippocampus, and cortex of ischemic brain. The down-regulation of cav-1 was correlated with the increased MMP-2 and -9 activities, decreased tight junction (TJ) protein zonula occludens (ZO)-1 expression and enhanced BBB permeability. Treatment of N G-nitro-l- arginine methyl ester [l-NAME, a non-selective nitric oxide synthase (NOS) inhibitor] reserved the expression of cav-1, inhibited MMPs activity, and reduced BBB permeability. To elucidate the roles of cav-1 in regulating MMPs and BBB permeability, we used two approaches including cav-1 knockdown in cultured brain microvascular endothelial cells (BMECs) in vitro and cav-1 knockout (KO) mice in vivo. Cav-1 knockdown remarkably increased MMPs activity in BMECs. Meanwhile, with focal cerebral ischemia-reperfusion, cav-1 deficiency mice displayed higher MMPs activities and BBB permeability than wild-type mice. Interestingly, the effects of l-NAME on MMPs activity and BBB permeability was partly reversed in cav-1 deficiency mice. These results, when taken together, suggest that cav-1 plays important roles in regulating MMPs activity and BBB permeability in focal cerebral ischemia and reperfusion injury. The effects of l-NAME on MMPs activity and BBB permeability are partly mediated by preservation of cav-1. © 2011 International Society for Neurochemistry.en_HK
dc.languageengen_US
dc.publisherBlackwell Publishing Ltd.-
dc.relation.ispartofJournal of Neurochemistryen_HK
dc.rightsThe definitive version is available at www.blackwell-synergy.com-
dc.subjectblood-brain barrieren_HK
dc.subjectcaveolin-1en_HK
dc.subjectischemiaen_HK
dc.subjectnitric oxide synthaseen_HK
dc.subject.meshBlood-Brain Barrier - physiopathologyen_US
dc.subject.meshBrain Ischemia - enzymology - physiopathologyen_US
dc.subject.meshCaveolin 1 - physiologyen_US
dc.subject.meshMatrix Metalloproteinases - metabolismen_US
dc.subject.meshReperfusion Injury - enzymology - physiopathologyen_US
dc.titleCaveolin-1 regulates nitric oxide-mediated matrix metalloproteinases activity and blood-brain barrier permeability in focal cerebral ischemia and reperfusion injuryen_HK
dc.typeArticleen_HK
dc.identifier.emailTong, Y: tongyao@hku.hken_HK
dc.identifier.emailChung, SK: skchung@hkucc.hku.hken_HK
dc.identifier.emailShen, J: shenjg@hku.hken_HK
dc.identifier.authorityTong, Y=rp00509en_HK
dc.identifier.authorityChung, SK=rp00381en_HK
dc.identifier.authorityShen, J=rp00487en_HK
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1111/j.1471-4159.2011.07542.xen_HK
dc.identifier.pmid22007835-
dc.identifier.scopuseid_2-s2.0-83755190692en_HK
dc.identifier.hkuros198757-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-83755190692&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume120en_HK
dc.identifier.issue1en_HK
dc.identifier.spage147en_HK
dc.identifier.epage156en_HK
dc.identifier.eissn1471-4159-
dc.identifier.isiWOS:000298060500015-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridGu, Y=37014467100en_HK
dc.identifier.scopusauthoridZheng, G=23969618100en_HK
dc.identifier.scopusauthoridXu, M=54394643900en_HK
dc.identifier.scopusauthoridLi, Y=26643036800en_HK
dc.identifier.scopusauthoridChen, X=54785889900en_HK
dc.identifier.scopusauthoridZhu, W=54786127100en_HK
dc.identifier.scopusauthoridTong, Y=9045384000en_HK
dc.identifier.scopusauthoridChung, SK=7404292976en_HK
dc.identifier.scopusauthoridLiu, KJ=7404200456en_HK
dc.identifier.scopusauthoridShen, J=7404929947en_HK

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats