PUBLICATION
Tanshinone I prevents atorvastatin-induced cerebral hemorrhage in zebrafish and stabilizes endothelial cell-cell adhesion by inhibiting VE-cadherin internalization and actin-myosin contractility
- Authors
- Huang, B., Zhou, Z.Y., Li, S., Huang, X.H., Tang, J.Y., Hoi, M.P.M., Lee, S.M.Y.
- ID
- ZDB-PUB-171012-4
- Date
- 2017
- Source
- Pharmacological research 128: 389-398 (Journal)
- Registered Authors
- Keywords
- Endothelial cell adhesion, HUVECs, Hemorrhagic stroke, Tanshinone I, Vascular integrity, Zebrafish
- MeSH Terms
-
- Abietanes/pharmacology*
- Actins/metabolism*
- Animals
- Animals, Genetically Modified
- Antigens, CD/metabolism*
- Atorvastatin
- Cadherins/metabolism*
- Cell Adhesion/drug effects
- Cerebral Hemorrhage/chemically induced
- Cerebral Hemorrhage/metabolism*
- Cerebral Hemorrhage/prevention & control
- Embryo, Nonmammalian
- Human Umbilical Vein Endothelial Cells/drug effects*
- Human Umbilical Vein Endothelial Cells/physiology
- Humans
- Myosins/metabolism*
- Protective Agents/pharmacology*
- Zebrafish/genetics
- PubMed
- 29017932 Full text @ Pharmacol. Res.
Citation
Huang, B., Zhou, Z.Y., Li, S., Huang, X.H., Tang, J.Y., Hoi, M.P.M., Lee, S.M.Y. (2017) 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.
Abstract
Defects 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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping