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Tanshinone I prevents atorvastatin-induced cerebral hemorrhage in zebrafish and stabilizes endothelial cell–cell adhesion by inhibiting VE-cadherin internalization and actin-myosin contractility
Huang B.1; Zhou Z.-Y.1; Li S.1; Huang X.-H.1; Tang J.-Y.2; Hoi M.P.M.1; Lee S.M.Y.1
2018-02-01
Source PublicationPharmacological Research
ISSN10961186 10436618
Volume128Pages:389-398
AbstractDefects in vascular integrity in cerebrovasculature lead to serious pathologies including hemorrhagic stroke. The stability of cell adhesion junctions and actin-myosin contractile machinery are two major determinants for the integrity of endothelial monolayer. Here we have evaluated the protective effects of tanshinone I (Tan I), a lipophilic compound presents in Salvia miltiorrhiza, against atorvastatin-induced cerebral hemorrhage in zebrafish in vivo, and further dissected the molecular mechanisms in HUVECs. We demonstrated that Tan I protected endothelial integrity by stabilizing cell–cell adhesion junctions via the inhibition of Src-mediated VE-cadherin internalization and subsequent junction-linked actin cytoskeleton depolymerization. In addition, Tan I inhibited ROCK-associated endothelial contractile machinery by dephosphorylating cofilin and MYPT1. These findings identified Tan I as an endothelial stabilizing agent and suggested Tan I as a potential treatment for vascular leakage in hemorrhagic stroke.
KeywordEndothelial cell adhesion Hemorrhagic stroke HUVECs Tanshinone I Vascular integrity Zebrafish
DOI10.1016/j.phrs.2017.09.025
URLView the original
Language英語
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Cited Times [WOS]:2   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionUniversity of Macau
Affiliation1.University of Macau
2.Shanghai University of Traditional Chinese Medicine
First Author AffilicationUniversity of Macau
Recommended Citation
GB/T 7714
Huang B.,Zhou Z.-Y.,Li S.,et al. Tanshinone I prevents atorvastatin-induced cerebral hemorrhage in zebrafish and stabilizes endothelial cell–cell adhesion by inhibiting VE-cadherin internalization and actin-myosin contractility[J]. Pharmacological Research,2018,128:389-398.
APA Huang B..,Zhou Z.-Y..,Li S..,Huang X.-H..,Tang J.-Y..,...&Lee S.M.Y..(2018).Tanshinone I prevents atorvastatin-induced cerebral hemorrhage in zebrafish and stabilizes endothelial cell–cell adhesion by inhibiting VE-cadherin internalization and actin-myosin contractility.Pharmacological Research,128,389-398.
MLA Huang B.,et al."Tanshinone I prevents atorvastatin-induced cerebral hemorrhage in zebrafish and stabilizes endothelial cell–cell adhesion by inhibiting VE-cadherin internalization and actin-myosin contractility".Pharmacological Research 128(2018):389-398.
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