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http://purl.uniprot.org/citations/23058350http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/23058350http://www.w3.org/2000/01/rdf-schema#comment"

Background

The cardiac renin-angiotensin system (RAS) has been implicated in mediating myocyte hypertrophy and remodeling, although the biochemical mechanisms responsible for regulating the local RAS are poorly understood. Caveolin-1 (Cav-1)/Cav-3 double-knockout mice display cardiac hypertrophy, and in vitro disruption of lipid rafts/caveolae using methyl-β-cyclodextrin (MβCD) abolishes cardiac protection.

Methods

In this study, neonatal rat ventricular myocytes (NRVM) were used to determine whether lipid rafts/caveolae may be involved in the regulation of angiotensinogen (Ao) gene expression, a substrate of the RAS system.

Results

Treatment with MβCD caused a time-dependent upregulation of Ao gene expression, which was associated with differential regulation of mitogen-activated protein (MAP) kinases ERK1/2, p38 and JNK phosphorylation. JNK was highly phosphorylated shortly after MβCD treatment (2-30 min), whereas marked activation of ERK1/2 and p38 occurred much later (2-4h). β1D-Integrin was required for MβCD-induced activation of the MAP kinases. Pharmacologic inhibition of ERK1/2 and JNK enhanced MβCD-induced Ao gene expression, whereas p38 blockade inhibited this response. Adenovirus-mediated expression of wild-type p38α enhanced MβCD-induced Ao gene expression; conversely expression of dominant negative p38α blocked the stimulatory effects of MβCD. Expression of Cav-3 siRNA stimulated Ao gene expression, whereas overexpression of Cav-3 was inhibitory. Cav-1 and Cav-3 expression levels were found to be positively regulated by p38, but unaffected by ERK1/2 and JNK.

Conclusion

Collectively, these studies indicate that lipid rafts/caveolae couple to Ao gene expression through a mechanism that involves β1-integrin and the differential actions of MAP kinase family members."xsd:string
http://purl.uniprot.org/citations/23058350http://purl.org/dc/terms/identifier"doi:10.1016/j.ijcard.2012.09.131"xsd:string
http://purl.uniprot.org/citations/23058350http://purl.uniprot.org/core/author"Feng H."xsd:string
http://purl.uniprot.org/citations/23058350http://purl.uniprot.org/core/author"Verma S.K."xsd:string
http://purl.uniprot.org/citations/23058350http://purl.uniprot.org/core/author"Nizamutdinov D."xsd:string
http://purl.uniprot.org/citations/23058350http://purl.uniprot.org/core/author"Glaser S.S."xsd:string
http://purl.uniprot.org/citations/23058350http://purl.uniprot.org/core/author"Dostal D.E."xsd:string
http://purl.uniprot.org/citations/23058350http://purl.uniprot.org/core/author"Foster D.M."xsd:string
http://purl.uniprot.org/citations/23058350http://purl.uniprot.org/core/author"Lal H."xsd:string
http://purl.uniprot.org/citations/23058350http://purl.uniprot.org/core/author"Golden H.B."xsd:string
http://purl.uniprot.org/citations/23058350http://purl.uniprot.org/core/author"Gerilechaogetu F."xsd:string
http://purl.uniprot.org/citations/23058350http://purl.uniprot.org/core/date"2013"xsd:gYear
http://purl.uniprot.org/citations/23058350http://purl.uniprot.org/core/name"Int J Cardiol"xsd:string
http://purl.uniprot.org/citations/23058350http://purl.uniprot.org/core/pages"436-445"xsd:string
http://purl.uniprot.org/citations/23058350http://purl.uniprot.org/core/title"Caveolin and beta1-integrin coordinate angiotensinogen expression in cardiac myocytes."xsd:string
http://purl.uniprot.org/citations/23058350http://purl.uniprot.org/core/volume"168"xsd:string
http://purl.uniprot.org/citations/23058350http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/23058350
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http://purl.uniprot.org/uniprot/#_P49134-mappedCitation-23058350http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/23058350
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http://purl.uniprot.org/uniprot/P49134http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/23058350
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