Abstract
The aim of this work was to investigate the coupling of human urotensin II (hU-II) to RhoA activation and regulation of RhoA-dependent functions. The use of the Rho-kinase inhibitor Y-27632 and the development of a membrane-permeant RhoA inhibitor (TAT-C3) allowed us to demonstrate that hU-II induced arterial smooth muscle contraction, actin stress fiber formation, and proliferation through the activation of the small GTPase RhoA and its downstream effector Rho-kinase.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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ADP Ribose Transferases / genetics
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ADP Ribose Transferases / metabolism
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ADP Ribose Transferases / pharmacology
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Amides / pharmacology
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Animals
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Aorta, Thoracic / cytology
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Aorta, Thoracic / metabolism
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Botulinum Toxins*
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Cell Division / drug effects
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Cells, Cultured
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Cytoskeleton / drug effects
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Cytoskeleton / metabolism
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Dose-Response Relationship, Drug
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Enzyme Activation / physiology
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Enzyme Inhibitors / pharmacology
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Humans
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In Vitro Techniques
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Intracellular Signaling Peptides and Proteins
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Muscle, Smooth, Vascular / cytology
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Muscle, Smooth, Vascular / drug effects
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Muscle, Smooth, Vascular / metabolism*
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Norepinephrine / antagonists & inhibitors
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Norepinephrine / pharmacology
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Potassium Chloride / pharmacology
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Protein Serine-Threonine Kinases / antagonists & inhibitors
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Protein Serine-Threonine Kinases / metabolism*
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Pyridines / pharmacology
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Rats
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Rats, Wistar
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / metabolism
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Recombinant Fusion Proteins / pharmacology
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Signal Transduction / drug effects
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Signal Transduction / physiology
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Urotensins / metabolism
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Urotensins / pharmacology*
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Vasoconstriction / drug effects
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Vasoconstriction / physiology*
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Vasoconstrictor Agents / antagonists & inhibitors
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Vasoconstrictor Agents / pharmacology
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rho-Associated Kinases
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rhoA GTP-Binding Protein / antagonists & inhibitors
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rhoA GTP-Binding Protein / metabolism*
Substances
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Amides
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Enzyme Inhibitors
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Intracellular Signaling Peptides and Proteins
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Pyridines
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Recombinant Fusion Proteins
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Urotensins
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Vasoconstrictor Agents
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Y 27632
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Potassium Chloride
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urotensin II
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ADP Ribose Transferases
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exoenzyme C3, Clostridium botulinum
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Protein Serine-Threonine Kinases
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rho-Associated Kinases
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Botulinum Toxins
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rhoA GTP-Binding Protein
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Norepinephrine