Schäfer, Marina

[["dc.bibliographiccitation.firstpage","881"],["dc.bibliographiccitation.issue","9"],["dc.bibliographiccitation.journal","Circulation"],["dc.bibliographiccitation.lastpage","897"],["dc.bibliographiccitation.volume","135"],["dc.contributor.author","Abu-Taha, Issam H."],["dc.contributor.author","Heijman, Jordi"],["dc.contributor.author","Hippe, Hans-Jörg"],["dc.contributor.author","Wolf, Nadine M."],["dc.contributor.author","El-Armouche, Ali"],["dc.contributor.author","Nikolaev, Viacheslav O."],["dc.contributor.author","Schäfer, Marina"],["dc.contributor.author","Würtz, Christina M."],["dc.contributor.author","Neef, Stefan"],["dc.contributor.author","Voigt, Niels"],["dc.contributor.author","Baczkó, István"],["dc.contributor.author","Varró, András"],["dc.contributor.author","Müller, Marion"],["dc.contributor.author","Meder, Benjamin"],["dc.contributor.author","Katus, Hugo A."],["dc.contributor.author","Spiger, Katharina"],["dc.contributor.author","Vettel, Christiane"],["dc.contributor.author","Lehmann, Lorenz H."],["dc.contributor.author","Backs, Johannes"],["dc.contributor.author","Skolnik, Edward Y."],["dc.contributor.author","Lutz, Susanne"],["dc.contributor.author","Dobrev, Dobromir"],["dc.contributor.author","Wieland, Thomas"],["dc.date.accessioned","2020-12-10T18:38:01Z"],["dc.date.available","2020-12-10T18:38:01Z"],["dc.date.issued","2017"],["dc.description.abstract","Background: Chronic heart failure (HF) is associated with altered signal transduction via -adrenoceptors and G proteins and with reduced cAMP formation. Nucleoside diphosphate kinases (NDPKs) are enriched at the plasma membrane of patients with end-stage HF, but the functional consequences of this are largely unknown, particularly for NDPK-C. Here, we investigated the potential role of NDPK-C in cardiac cAMP formation and contractility. Methods: Real-time polymerase chain reaction, (far) Western blot, immunoprecipitation, and immunocytochemistry were used to study the expression, interaction with G proteins, and localization of NDPKs. cAMP levels were determined with immunoassays or fluorescent resonance energy transfer, and contractility was determined in cardiomyocytes (cell shortening) and in vivo (fractional shortening). Results: NDPK-C was essential for the formation of an NDPK-B/G protein complex. Protein and mRNA levels of NDPK-C were upregulated in end-stage human HF, in rats after long-term isoprenaline stimulation through osmotic minipumps, and after incubation of rat neonatal cardiomyocytes with isoprenaline. Isoprenaline also promoted translocation of NDPK-C to the plasma membrane. Overexpression of NDPK-C in cardiomyocytes increased cAMP levels and sensitized cardiomyocytes to isoprenaline-induced augmentation of contractility, whereas NDPK-C knockdown decreased cAMP levels. In vivo, depletion of NDPK-C in zebrafish embryos caused cardiac edema and ventricular dysfunction. NDPK-B knockout mice had unaltered NDPK-C expression but showed contractile dysfunction and exacerbated cardiac remodeling during long-term isoprenaline stimulation. In human end-stage HF, the complex formation between NDPK-C and G(i2) was increased whereas the NDPK-C/G(s) interaction was decreased, producing a switch that may contribute to an NDPK-C-dependent cAMP reduction in HF. Conclusions: Our findings identify NDPK-C as an essential requirement for both the interaction between NDPK isoforms and between NDPK isoforms and G proteins. NDPK-C is a novel critical regulator of -adrenoceptor/cAMP signaling and cardiac contractility. By switching from G(s) to G(i2) activation, NDPK-C may contribute to lower cAMP levels and the related contractile dysfunction in HF."],["dc.identifier.doi","10.1161/CIRCULATIONAHA.116.022852"],["dc.identifier.eissn","1524-4539"],["dc.identifier.isi","000395549700016"],["dc.identifier.issn","0009-7322"],["dc.identifier.pmid","27927712"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/77166"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Lippincott Williams & Wilkins"],["dc.relation.issn","1524-4539"],["dc.relation.issn","0009-7322"],["dc.title","Nucleoside Diphosphate Kinase-C Suppresses cAMP Formation in Human Heart Failure"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]