| http://purl.uniprot.org/citations/29187535 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/29187535 | http://www.w3.org/2000/01/rdf-schema#comment | "Duchenne muscular dystrophy (DMD) is an X-linked disorder with dystrophin loss that results in skeletal and cardiac muscle weakening and early death. Loss of the dystrophin-sarcoglycan complex delocalizes nitric oxide synthase (NOS) to alter its signaling, and augments mechanosensitive intracellular Ca2+ influx. The latter has been coupled to hyperactivation of the nonselective cation channel, transient receptor potential canonical channel 6 (Trpc6), in isolated myocytes. As Ca2+ also activates NOS, we hypothesized that Trpc6 would help to mediate nitric oxide (NO) dysregulation and that this would be manifest in increased myocardial S-nitrosylation, a posttranslational modification increasingly implicated in neurodegenerative, inflammatory, and muscle disease. Using a recently developed dual-labeling proteomic strategy, we identified 1,276 S-nitrosylated cysteine residues [S-nitrosothiol (SNO)] on 491 proteins in resting hearts from a mouse model of DMD (dmdmdx:utrn+/-). These largely consisted of mitochondrial proteins, metabolic regulators, and sarcomeric proteins, with 80% of them also modified in wild type (WT). S-nitrosylation levels, however, were increased in DMD. Genetic deletion of Trpc6 in this model (dmdmdx:utrn+/-:trpc6-/-) reversed ∼70% of these changes. Trpc6 deletion also ameliorated left ventricular dilation, improved cardiac function, and tended to reduce fibrosis. Furthermore, under catecholamine stimulation, which also increases NO synthesis and intracellular Ca2+ along with cardiac workload, the hypernitrosylated state remained as it did at baseline. However, the impact of Trpc6 deletion on the SNO proteome became less marked. These findings reveal a role for Trpc6-mediated hypernitrosylation in dmdmdx:utrn+/- mice and support accumulating evidence that implicates nitrosative stress in cardiac and muscle disease."xsd:string |
| http://purl.uniprot.org/citations/29187535 | http://purl.org/dc/terms/identifier | "doi:10.1073/pnas.1712623114"xsd:string |
| http://purl.uniprot.org/citations/29187535 | http://purl.uniprot.org/core/author | "Chung H.S."xsd:string |
| http://purl.uniprot.org/citations/29187535 | http://purl.uniprot.org/core/author | "Zhu G."xsd:string |
| http://purl.uniprot.org/citations/29187535 | http://purl.uniprot.org/core/author | "Van Eyk J.E."xsd:string |
| http://purl.uniprot.org/citations/29187535 | http://purl.uniprot.org/core/author | "Kim G.E."xsd:string |
| http://purl.uniprot.org/citations/29187535 | http://purl.uniprot.org/core/author | "Kass D.A."xsd:string |
| http://purl.uniprot.org/citations/29187535 | http://purl.uniprot.org/core/author | "Bedja D."xsd:string |
| http://purl.uniprot.org/citations/29187535 | http://purl.uniprot.org/core/author | "Venkatraman V."xsd:string |
| http://purl.uniprot.org/citations/29187535 | http://purl.uniprot.org/core/author | "Holewinski R.J."xsd:string |
| http://purl.uniprot.org/citations/29187535 | http://purl.uniprot.org/core/date | "2017"xsd:gYear |
| http://purl.uniprot.org/citations/29187535 | http://purl.uniprot.org/core/name | "Proc Natl Acad Sci U S A"xsd:string |
| http://purl.uniprot.org/citations/29187535 | http://purl.uniprot.org/core/pages | "E10763-E10771"xsd:string |
| http://purl.uniprot.org/citations/29187535 | http://purl.uniprot.org/core/title | "Transient receptor potential channel 6 regulates abnormal cardiac S-nitrosylation in Duchenne muscular dystrophy."xsd:string |
| http://purl.uniprot.org/citations/29187535 | http://purl.uniprot.org/core/volume | "114"xsd:string |
| http://purl.uniprot.org/citations/29187535 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/29187535 |
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