| http://purl.uniprot.org/citations/34558218 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/34558218 | http://www.w3.org/2000/01/rdf-schema#comment | "Catecholaminergic polymorphic ventricular tachycardia type 1 (CPVT1) is an inherited arrhythmogenic disorder caused by missense mutations in the cardiac ryanodine receptors (RyR2), that result in increased β-adrenoceptor stimulation-induced diastolic Ca2+ leak. We have previously shown that exercise training prevents arrhythmias in CPVT1, potentially by reducing the oxidation of Ca2+ /calmodulin-dependent protein kinase type II (CaMKII). Therefore, we tested whether an oxidation-resistant form of CaMKII protects mice carrying the CPVT1-causative mutation RyR2-R2474S (RyR2-RS) against arrhythmias. Antioxidant treatment (N-acetyl-L-cysteine) reduced the frequency of β-adrenoceptor stimulation-induced arrhythmogenic Ca2+ waves in isolated cardiomyocytes from RyR2-RS mice. To test whether the prevention of CaMKII oxidation exerts an antiarrhythmic effect, mice expressing the oxidation-resistant CaMKII-MM281/282VV variant (MMVV) were crossed with RyR2-RS mice to create a double transgenic model (RyR2-RS/MMVV). Wild-type mice served as controls. Telemetric ECG surveillance revealed an increased incidence of ventricular tachycardia and an increased arrhythmia score in both RyR2-RS and RyR2-RS/MMVV compared to wild-type mice, both following a β-adrenoceptor challenge (isoprenaline i.p.), and following treadmill exercise combined with a β-adrenoceptor challenge. There were no differences in the incidence of arrhythmias between RyR2-RS and RyR2-RS/MMVV mice. Furthermore, no differences were observed in β-adrenoceptor stimulation-induced Ca2+ waves in RyR2-RS/MMVV compared to RyR2-RS. In conclusion, antioxidant treatment reduces β-adrenoceptor stimulation-induced Ca2+ waves in RyR2-RS cardiomyocytes. However, oxidation-resistant CaMKII-MM281/282VV does not protect RyR2-RS mice from β-adrenoceptor stimulation-induced Ca2+ waves or arrhythmias. Hence, alternative oxidation-sensitive targets need to be considered to explain the beneficial effect of antioxidant treatment on Ca2+ waves in cardiomyocytes from RyR2-RS mice."xsd:string |
| http://purl.uniprot.org/citations/34558218 | http://purl.org/dc/terms/identifier | "doi:10.14814/phy2.15030"xsd:string |
| http://purl.uniprot.org/citations/34558218 | http://purl.uniprot.org/core/author | "Anderson M.E."xsd:string |
| http://purl.uniprot.org/citations/34558218 | http://purl.uniprot.org/core/author | "Sjaastad I."xsd:string |
| http://purl.uniprot.org/citations/34558218 | http://purl.uniprot.org/core/author | "Lehnart S.E."xsd:string |
| http://purl.uniprot.org/citations/34558218 | http://purl.uniprot.org/core/author | "Stokke M.K."xsd:string |
| http://purl.uniprot.org/citations/34558218 | http://purl.uniprot.org/core/author | "Manotheepan R."xsd:string |
| http://purl.uniprot.org/citations/34558218 | http://purl.uniprot.org/core/author | "Sadredini M."xsd:string |
| http://purl.uniprot.org/citations/34558218 | http://purl.uniprot.org/core/date | "2021"xsd:gYear |
| http://purl.uniprot.org/citations/34558218 | http://purl.uniprot.org/core/name | "Physiol Rep"xsd:string |
| http://purl.uniprot.org/citations/34558218 | http://purl.uniprot.org/core/pages | "e15030"xsd:string |
| http://purl.uniprot.org/citations/34558218 | http://purl.uniprot.org/core/title | "The oxidation-resistant CaMKII-MM281/282VV mutation does not prevent arrhythmias in CPVT1."xsd:string |
| http://purl.uniprot.org/citations/34558218 | http://purl.uniprot.org/core/volume | "9"xsd:string |
| http://purl.uniprot.org/citations/34558218 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/34558218 |
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