| http://purl.uniprot.org/citations/18662195 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/18662195 | http://www.w3.org/2000/01/rdf-schema#comment | "Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a disorder of cardiomyocyte intercalated disk proteins causing sudden death. Heterozygous mutations of the desmosomal protein plakophilin-2 (PKP-2) are the commonest genetic cause of ARVC. Abnormal gap junction connexin43 expression has been reported in autosomal dominant forms of ARVC (Naxos and Carvajal disease) caused by homozygous mutations of desmosomal plakoglobin and desmoplakin. In tissue culture, suppression of PKP-2 results in decreased expression of connexin43. We sought to characterize the expression and localization of connexin43 in patients with ARVC secondary to heterozygous PKP-2 mutations. Complete PKP-2 gene sequencing of 27 ARVC patients was utilized to identify mutant genotypes. Endomyocardial biopsies of identified carriers were then assessed by immunofluorescence to visualize intercalated disk proteins. N-cadherin was targeted to highlight intercalated disks, followed by counterstaining for PKP-2 or connexin43 using confocal double immunofluorescence microscopy. Immunofluorescence was quantified using an AdobeA Photoshop protocol, and colocalization coefficients were determined. PKP-2 siRNA experiments were performed in mouse cardiomyocyte (HL1) cell culture with Western blot analysis to assess connexin43 expression following PKP-2 suppression. Missense and frameshift mutations of the PKP-2 gene were found in four patients with biopsy material available for analysis. Immunofluorescent studies showed PKP-2 localization to the intercalated disk despite mutations, but associated with decreased connexin43 expression and abnormal colocalization. PKP-2 siRNA in HL1 culture confirmed decreased connexin43 expression. Reduced connexin43 expression and localization to the intercalated disk occurs in heterozygous human PKP-2 mutations, potentially explaining the delayed conduction and propensity to develop arrhythmias seen in this disease."xsd:string |
| http://purl.uniprot.org/citations/18662195 | http://purl.org/dc/terms/identifier | "doi:10.1111/j.1582-4934.2008.00438.x"xsd:string |
| http://purl.uniprot.org/citations/18662195 | http://purl.uniprot.org/core/author | "Cui X."xsd:string |
| http://purl.uniprot.org/citations/18662195 | http://purl.uniprot.org/core/author | "Liu F."xsd:string |
| http://purl.uniprot.org/citations/18662195 | http://purl.uniprot.org/core/author | "Scherer S.W."xsd:string |
| http://purl.uniprot.org/citations/18662195 | http://purl.uniprot.org/core/author | "Wilson G.J."xsd:string |
| http://purl.uniprot.org/citations/18662195 | http://purl.uniprot.org/core/author | "Taylor G.P."xsd:string |
| http://purl.uniprot.org/citations/18662195 | http://purl.uniprot.org/core/author | "Hamilton R.M."xsd:string |
| http://purl.uniprot.org/citations/18662195 | http://purl.uniprot.org/core/author | "Fidler L.M."xsd:string |
| http://purl.uniprot.org/citations/18662195 | http://purl.uniprot.org/core/date | "2009"xsd:gYear |
| http://purl.uniprot.org/citations/18662195 | http://purl.uniprot.org/core/name | "J Cell Mol Med"xsd:string |
| http://purl.uniprot.org/citations/18662195 | http://purl.uniprot.org/core/pages | "4219-4228"xsd:string |
| http://purl.uniprot.org/citations/18662195 | http://purl.uniprot.org/core/title | "Abnormal connexin43 in arrhythmogenic right ventricular cardiomyopathy caused by plakophilin-2 mutations."xsd:string |
| http://purl.uniprot.org/citations/18662195 | http://purl.uniprot.org/core/volume | "13"xsd:string |
| http://purl.uniprot.org/citations/18662195 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/18662195 |
| http://purl.uniprot.org/citations/18662195 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/18662195 |
| http://purl.uniprot.org/uniprot/#_A0A654IBU3-mappedCitation-18662195 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/18662195 |
| http://purl.uniprot.org/uniprot/#_B4DGM6-mappedCitation-18662195 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/18662195 |
| http://purl.uniprot.org/uniprot/#_B4DI81-mappedCitation-18662195 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/18662195 |
| http://purl.uniprot.org/uniprot/#_B4DMC9-mappedCitation-18662195 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/18662195 |
| http://purl.uniprot.org/uniprot/#_B4DR79-mappedCitation-18662195 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/18662195 |
| http://purl.uniprot.org/uniprot/#_B4DN47-mappedCitation-18662195 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/18662195 |
| http://purl.uniprot.org/uniprot/#_B4DN50-mappedCitation-18662195 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/18662195 |
| http://purl.uniprot.org/uniprot/#_B8QGS8-mappedCitation-18662195 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/18662195 |