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http://purl.uniprot.org/citations/26562480http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/26562480http://www.w3.org/2000/01/rdf-schema#comment"

Background and purpose

Angiotensin II (AngII) induces migration and growth of vascular smooth muscle cell (VSMC), which is responsible for vascular remodelling in some cardiovascular diseases. Ang II also activates a Cl(-) current, but the underlying mechanism is not clear.

Experimental approach

The A10 cell line and primary cultures of VSMC from control, ClC-3 channel null mice and WT mice made hypertensive with AngII infusions were used. Techniques employed included whole-cell patch clamp, co-immunoprecipitation, site-specific mutagenesis and Western blotting,

Key results

In VSMC, AngII induced Cl(-) currents was carried by the chloride ion channel ClC-3. This current was absent in VSMC from ClC-3 channel null mice. The AngII-induced Cl(-) current involved interactions between ClC-3 channels and Rho-kinase 2 (ROCK2), shown by N- or C-terminal truncation of ClC-3 protein, ROCK2 siRNA and co-immunoprecipitation assays. Phosphorylation of ClC-3 channels at Thr(532) by ROCK2 was critical for AngII-induced Cl(-) current and VSMC migration. The ClC-3 T532D mutant (mutation of Thr(532) to aspartate), mimicking phosphorylated ClC-3 protein, significantly potentiated AngII-induced Cl(-) current and VSMC migration, while ClC-3 T532A (mutation of Thr(532) to alanine) had the opposite effects. AngII-induced cell migration was markedly decreased in VSMC from ClC-3 channel null mice that was insensitive to Y27632, an inhibitor of ROCK2. In addition, AngII-induced cerebrovascular remodelling was decreased in ClC-3 null mice, possibly by the ROCK2 pathway.

Conclusions and implications

ClC-3 protein phosphorylation at Thr(532) by ROCK2 is required for AngII-induced Cl(-) current and VSMC migration that are involved in AngII-induced vascular remodelling in hypertension."xsd:string
http://purl.uniprot.org/citations/26562480http://purl.org/dc/terms/identifier"doi:10.1111/bph.13385"xsd:string
http://purl.uniprot.org/citations/26562480http://purl.uniprot.org/core/author"Gao M."xsd:string
http://purl.uniprot.org/citations/26562480http://purl.uniprot.org/core/author"Sun L."xsd:string
http://purl.uniprot.org/citations/26562480http://purl.uniprot.org/core/author"Wang G.L."xsd:string
http://purl.uniprot.org/citations/26562480http://purl.uniprot.org/core/author"Liu C.Z."xsd:string
http://purl.uniprot.org/citations/26562480http://purl.uniprot.org/core/author"Lin C.X."xsd:string
http://purl.uniprot.org/citations/26562480http://purl.uniprot.org/core/author"Zhou J.G."xsd:string
http://purl.uniprot.org/citations/26562480http://purl.uniprot.org/core/author"Tang Y.B."xsd:string
http://purl.uniprot.org/citations/26562480http://purl.uniprot.org/core/author"Ma M.M."xsd:string
http://purl.uniprot.org/citations/26562480http://purl.uniprot.org/core/author"Guan Y.Y."xsd:string
http://purl.uniprot.org/citations/26562480http://purl.uniprot.org/core/date"2016"xsd:gYear
http://purl.uniprot.org/citations/26562480http://purl.uniprot.org/core/name"Br J Pharmacol"xsd:string
http://purl.uniprot.org/citations/26562480http://purl.uniprot.org/core/pages"529-544"xsd:string
http://purl.uniprot.org/citations/26562480http://purl.uniprot.org/core/title"Threonine532 phosphorylation in ClC-3 channels is required for angiotensin II-induced Cl(-) current and migration in cultured vascular smooth muscle cells."xsd:string
http://purl.uniprot.org/citations/26562480http://purl.uniprot.org/core/volume"173"xsd:string
http://purl.uniprot.org/citations/26562480http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/26562480
http://purl.uniprot.org/citations/26562480http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/26562480
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http://purl.uniprot.org/uniprot/#_Q6PEV2-mappedCitation-26562480http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/26562480
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