Nikolaev, Viacheslav O.

[["dc.bibliographiccitation.journal","Circulation Research"],["dc.contributor.author","Berisha, Filip"],["dc.contributor.author","Götz, Konrad"],["dc.contributor.author","Wegener, Jörg W."],["dc.contributor.author","Brandenburg, Sören"],["dc.contributor.author","Subramanian, Hariharan"],["dc.contributor.author","Molina, Cristina E."],["dc.contributor.author","Rueffer, Andre"],["dc.contributor.author","Petersen, Johannes"],["dc.contributor.author","Bernhardt, Alexander"],["dc.contributor.author","Nikolaev, Viacheslav O."],["dc.date.accessioned","2021-06-01T10:47:48Z"],["dc.date.available","2021-06-01T10:47:48Z"],["dc.date.issued","2021"],["dc.description.abstract","Rationale: 3',5'-cyclic adenosine monophosphate (cAMP) is a ubiquitous second messenger which, upon β-adrenergic receptor (β-AR) stimulation, acts in microdomains to regulate cardiac excitation-contraction coupling by activating phosphorylation of calcium handling proteins. One crucial microdomain is in vicinity of the cardiac ryanodine receptor type 2 (RyR2) which is associated with arrhythmogenic diastolic calcium leak from the sarcoplasmic reticulum (SR) often occurring in heart failure. Objective: We sought to establish a real time live cell imaging approach capable of directly visualizing cAMP in the vicinity of mouse and human RyR2 and to analyze its pathological changes in failing cardiomyocytes under β-AR stimulation. Methods and Results: We generated a novel targeted fluorescent biosensor Epac1-JNC for RyR2-associated cAMP and expressed it in transgenic mouse hearts as well in human ventricular myocytes using adenoviral gene transfer. In healthy cardiomyocytes, β 1 -AR but not β 2 -AR stimulation strongly increased local RyR2-associated cAMP levels. However, already in cardiac hypertrophy induced by aortic banding, there was a marked subcellular redistribution of phosphodiesterases (PDEs) 2, 3 and 4, which included a dramatic loss of the local pool of PDE4. This was also accompanied by measurableβ2-AR/AMP signals in the vicinity of RyR2 in failing mouse and human myocytes, increased β2-AR-dependent RyR2 phosphorylation, SR calcium leak and arrhythmia susceptibility. Conclusions: Our new imaging approach could visualize cAMP levels in the direct vicinity of cardiac RyR2. Unexpectedly, in mouse and human failing myocytes, it could uncover functionally relevant local arrhythmogenic β2-AR/cAMP signals which might be an interesting antiarrhythmic target for heart failure."],["dc.identifier.doi","10.1161/CIRCRESAHA.120.318234"],["dc.identifier.pmid","33902292"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/85724"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/393"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-425"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation.eissn","1524-4571"],["dc.relation.issn","0009-7330"],["dc.relation.workinggroup","RG Brandenburg"],["dc.relation.workinggroup","RG Hasenfuß (Transition zur Herzinsuffizienz)"],["dc.relation.workinggroup","RG Lehnart (Cellular Biophysics and Translational Cardiology Section)"],["dc.relation.workinggroup","RG Nikolaev (Cardiovascular Research Center)"],["dc.title","cAMP Imaging at Ryanodine Receptors Reveals β2-Adrenoceptor Driven Arrhythmias"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","S63"],["dc.bibliographiccitation.journal","European Journal of Heart Failure"],["dc.bibliographiccitation.lastpage","S64"],["dc.bibliographiccitation.volume","12"],["dc.contributor.author","Mehel, Hind"],["dc.contributor.author","Emons, J."],["dc.contributor.author","Vettel, Christiane"],["dc.contributor.author","Lechene, Patrick"],["dc.contributor.author","Maier, Lars. S."],["dc.contributor.author","Nikolaev, V. O."],["dc.contributor.author","Vandecasteele, Gregoire"],["dc.contributor.author","Fischmeister, Rodolphe"],["dc.contributor.author","Elarmouche, A."],["dc.date.accessioned","2018-11-07T09:25:42Z"],["dc.date.available","2018-11-07T09:25:42Z"],["dc.date.issued","2013"],["dc.identifier.isi","000332489100237"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/30127"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-blackwell"],["dc.publisher.place","Hoboken"],["dc.title","Phoshodiesterase-2 is Upregulated in Human Failing Hearts and Blunts Beta-Adrenergic Responses in Cardiomyocytes"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","European Journal of Heart Failure"],["dc.bibliographiccitation.volume","12"],["dc.contributor.author","Perera, Ruwan K."],["dc.contributor.author","Nikolaev, V. O."],["dc.date.accessioned","2018-11-07T09:25:43Z"],["dc.date.available","2018-11-07T09:25:43Z"],["dc.date.issued","2013"],["dc.identifier.isi","000332489100184"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/30130"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-blackwell"],["dc.publisher.place","Hoboken"],["dc.title","FRET measurements of local cAMP signaling in the sarcolemmal/T- tubular compartment of cardiomyocytes"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","21"],["dc.bibliographiccitation.journal","Circulation"],["dc.bibliographiccitation.volume","126"],["dc.contributor.author","Wright, Peter T."],["dc.contributor.author","Diakonov, Ivan"],["dc.contributor.author","Nikolaev, Viacheslav O."],["dc.contributor.author","Lyon, Alexander R."],["dc.contributor.author","Harding, Sian E."],["dc.contributor.author","Gorelik, Julia"],["dc.date.accessioned","2018-11-07T09:03:20Z"],["dc.date.available","2018-11-07T09:03:20Z"],["dc.date.issued","2012"],["dc.identifier.isi","000208885005271"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/24886"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Lippincott Williams & Wilkins"],["dc.publisher.place","Philadelphia"],["dc.relation.issn","1524-4539"],["dc.relation.issn","0009-7322"],["dc.title","Myocardial Gradients in Caveolar Number Modulate Cardiomyocyte Contractile Response to Specific beta 2AR Stimulation"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1163"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Human Molecular Genetics"],["dc.bibliographiccitation.lastpage","1174"],["dc.bibliographiccitation.volume","23"],["dc.contributor.author","Cazabat, Laure"],["dc.contributor.author","Ragazzon, Bruno"],["dc.contributor.author","Varin, Audrey"],["dc.contributor.author","Potier-Cartereau, Marie"],["dc.contributor.author","Vandier, Christophe"],["dc.contributor.author","Vezzosi, Delphine"],["dc.contributor.author","Risk-Rabin, Marthe"],["dc.contributor.author","Guellich, Aziz"],["dc.contributor.author","Schittl, Julia"],["dc.contributor.author","Lechene, Patrick"],["dc.contributor.author","Richter, Wito"],["dc.contributor.author","Nikolaev, Viacheslav O."],["dc.contributor.author","Zhang, J."],["dc.contributor.author","Bertherat, Jerome"],["dc.contributor.author","Vandecasteele, Gregoire"],["dc.date.accessioned","2018-11-07T09:43:24Z"],["dc.date.available","2018-11-07T09:43:24Z"],["dc.date.issued","2014"],["dc.description.abstract","Carney complex (CNC) is a hereditary disease associating cardiac myxoma, spotty skin pigmentation and endocrine overactivity. CNC is caused by inactivating mutations in the PRKAR1A gene encoding PKA type I alpha regulatory subunit (RI alpha). Although PKA activity is enhanced in CNC, the mechanisms linking PKA dysregulation to endocrine tumorigenesis are poorly understood. In this study, we used Forster resonance energy transfer (FRET)-based sensors for cAMP and PKA activity to define the role of RI alpha in the spatiotemporal organization of the cAMP/PKA pathway. RI alpha knockdown in HEK293 cells increased basal as well as forskolin or prostaglandin E-1 (PGE(1))-stimulated total cellular PKA activity as reported by western blots of endogenous PKA targets and the FRET-based global PKA activity reporter, AKAR3. Using variants of AKAR3 targeted to subcellular compartments, we identified similar increases in the response to PGE(1) in the cytoplasm and at the outer mitochondrial membrane. In contrast, at the plasma membrane, the response to PGE(1) was decreased along with an increase in basal FRET ratio. These results were confirmed by western blot analysis of basal and PGE(1)-induced phosphorylation of membrane-associated vasodilator-stimulated phosphoprotein. Similar differences were observed between the cytoplasm and the plasma membrane in human adrenal cells carrying a RI alpha inactivating mutation. RI alpha inactivation also increased cAMP in the cytoplasm, at the outer mitochondrial membrane and at the plasma membrane, as reported by targeted versions of the cAMP indicator Epac1-camps. These results show that RI alpha inactivation leads to multiple, compartment-specific alterations of the cAMP/PKA pathway revealing new aspects of signaling dysregulation in tumorigenesis."],["dc.identifier.doi","10.1093/hmg/ddt510"],["dc.identifier.isi","000331815000004"],["dc.identifier.pmid","24122441"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/34177"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Oxford Univ Press"],["dc.relation.issn","1460-2083"],["dc.relation.issn","0964-6906"],["dc.title","Inactivation of the Carney complex gene 1 (PRKAR1A) alters spatiotemporal regulation of cAMP and cAMP-dependent protein kinase: a study using genetically encoded FRET-based reporters"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","22"],["dc.bibliographiccitation.journal","Circulation"],["dc.bibliographiccitation.volume","128"],["dc.contributor.author","O'Hara, Thomas"],["dc.contributor.author","Wright, Peter T."],["dc.contributor.author","Nikolaev, Viacheslav O."],["dc.contributor.author","Gorelik, Julia"],["dc.contributor.author","Trayanova, Natalia A."],["dc.date.accessioned","2018-11-07T09:17:26Z"],["dc.date.available","2018-11-07T09:17:26Z"],["dc.date.issued","2013"],["dc.identifier.isi","000332162901136"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/28172"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Lippincott Williams & Wilkins"],["dc.publisher.place","Philadelphia"],["dc.relation.conference","Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association"],["dc.relation.eventlocation","Dallas, TX"],["dc.relation.issn","1524-4539"],["dc.relation.issn","0009-7322"],["dc.title","Caveolin-3 Restores Local cAMP Signaling Without Restoring T-Tubules in Response to ss 2 Adrenergic Receptor Stimulation in Heart Failure"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","6965"],["dc.bibliographiccitation.journal","Nature Communications"],["dc.bibliographiccitation.volume","6"],["dc.contributor.author","Sprenger, Julia U."],["dc.contributor.author","Perera, Ruwan K."],["dc.contributor.author","Steinbrecher, Julia H."],["dc.contributor.author","Lehnart, Stephan E."],["dc.contributor.author","Maier, Lars S."],["dc.contributor.author","Hasenfuß, Gerd"],["dc.contributor.author","Nikolaev, Viacheslav O."],["dc.date.accessioned","2017-09-07T11:44:27Z"],["dc.date.available","2017-09-07T11:44:27Z"],["dc.date.issued","2015"],["dc.description.abstract","3',5'-cyclic adenosine monophosphate (cAMP) is an ubiquitous second messenger that regulates physiological functions by acting in distinct subcellular microdomains. Although several targeted cAMP biosensors are developed and used in single cells, it is unclear whether such biosensors can be successfully applied in vivo, especially in the context of disease. Here, we describe a transgenic mouse model expressing a targeted cAMP sensor and analyse microdomain-specific second messenger dynamics in the vicinity of the sarcoplasmic/endoplasmic reticulum calcium ATPase (SERCA). We demonstrate the bio-compatibility of this targeted sensor and its potential for real-time monitoring of compartmentalized cAMP signalling in adult cardiomyocytes isolated from a healthy mouse heart and from an in vivo cardiac disease model. In particular, we uncover the existence of a phos-phodiesterase-dependent receptor-microdomain communication, which is affected in hypertrophy, resulting in reduced beta-adrenergic receptor-cAMP signalling to SERCA."],["dc.identifier.doi","10.1038/ncomms7965"],["dc.identifier.gro","3141928"],["dc.identifier.isi","000353704700017"],["dc.identifier.pmid","25917898"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/2634"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/103"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation","SFB 1002 | A01: cAMP- und cGMP- Mikrodomänen bei Herzhypertrophie und Insuffizienz"],["dc.relation","SFB 1002 | A09: Lokale molekulare Nanodomänen-Regulation der kardialen Ryanodin-Rezeptor-Funktion"],["dc.relation.issn","2041-1723"],["dc.relation.workinggroup","RG Hasenfuß (Transition zur Herzinsuffizienz)"],["dc.relation.workinggroup","RG L. Maier (Experimentelle Kardiologie)"],["dc.relation.workinggroup","RG Nikolaev (Cardiovascular Research Center)"],["dc.relation.workinggroup","RG Lehnart (Cellular Biophysics and Translational Cardiology Section)"],["dc.title","In vivo model with targeted cAMP biosensor reveals changes in receptor-microdomain communication in cardiac disease"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","357"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Circulation Heart Failure"],["dc.bibliographiccitation.lastpage","365"],["dc.bibliographiccitation.volume","5"],["dc.contributor.author","Lyon, Alexander R."],["dc.contributor.author","Nikolaev, Viacheslav O."],["dc.contributor.author","Miragoli, Michele"],["dc.contributor.author","Sikkel, Markus B."],["dc.contributor.author","Paur, Helen"],["dc.contributor.author","Benard, Ludovic"],["dc.contributor.author","Hulot, Jean-Sebastien"],["dc.contributor.author","Kohlbrenner, Erik"],["dc.contributor.author","Hajjar, Roger J."],["dc.contributor.author","Peters, Nicholas S."],["dc.contributor.author","Korchev, Yuri E."],["dc.contributor.author","Macleod, Ken T."],["dc.contributor.author","Harding, Sian E."],["dc.contributor.author","Gorelik, Julia"],["dc.date.accessioned","2018-11-07T09:10:31Z"],["dc.date.available","2018-11-07T09:10:31Z"],["dc.date.issued","2012"],["dc.description.abstract","Background-Cardiomyocyte surface morphology and T-tubular structure are significantly disrupted in chronic heart failure, with important functional sequelae, including redistribution of sarcolemmal beta(2)-adrenergic receptors (beta(2)AR) and localized secondary messenger signaling. Plasticity of these changes in the reverse remodeled failing ventricle is unknown. We used AAV9.SERCA2a gene therapy to rescue failing rat hearts and measured z-groove index, T-tubule density, and compartmentalized beta(2)AR-mediated cAMP signals, using a combined nanoscale scanning ion conductance microscopy-Forster resonance energy transfer technique. Methods and Results-Cardiomyocyte surface morphology, quantified by z-groove index and T-tubule density, was normalized in reverse-remodeled hearts after SERCA2a gene therapy. Recovery of sarcolemmal microstructure correlated with functional beta(2)AR redistribution back into the z-groove and T-tubular network, whereas minimal cAMP responses were initiated after local beta(2)AR stimulation of crest membrane, as observed in failing cardiomyocytes. Improvement of beta(2)AR localization was associated with recovery of beta AR-stimulated contractile responses in rescued cardiomyocytes. Retubulation was associated with reduced spatial heterogeneity of electrically stimulated calcium transients and recovery of myocardial BIN-1 and TCAP protein expression but not junctophilin-2. Conclusions-In summary, abnormalities of sarcolemmal structure in heart failure show plasticity with reappearance of z-grooves and T-tubules in reverse-remodeled hearts. Recovery of surface topology is necessary for normalization of beta(2)AR location and signaling responses. (Circ Heart Fail. 2012;5:357-365.)"],["dc.identifier.doi","10.1161/CIRCHEARTFAILURE.111.964692"],["dc.identifier.isi","000313577100011"],["dc.identifier.pmid","22456061"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/26510"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Lippincott Williams & Wilkins"],["dc.relation.issn","1941-3289"],["dc.title","Plasticity of Surface Structures and beta(2)-Adrenergic Receptor Localization in Failing Ventricular Cardiomyocytes During Recovery From Heart Failure"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","American Journal of Respiratory and Critical Care Medicine"],["dc.bibliographiccitation.volume","193"],["dc.contributor.author","Zuo, H."],["dc.contributor.author","Poppinga, W. J."],["dc.contributor.author","Zeisberg, Elisabeth M."],["dc.contributor.author","Nikolaev, V. O."],["dc.contributor.author","Schmidt, M."],["dc.date.accessioned","2018-11-07T10:19:43Z"],["dc.date.available","2018-11-07T10:19:43Z"],["dc.date.issued","2016"],["dc.identifier.isi","000390749605531"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/41719"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Thoracic Soc"],["dc.publisher.place","New york"],["dc.relation.conference","International Conference of the American-Thoracic-Society (ATS)"],["dc.relation.eventlocation","San Francisco, CA"],["dc.title","Monitoring Local Pulmonary Camp Levels: Combining Precision Cut Lung Slice (pcls) And Fluorescence Resonance Energy Transfer (fret) Technologies In Mice"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","121"],["dc.bibliographiccitation.lastpage","129"],["dc.bibliographiccitation.seriesnr","1020"],["dc.contributor.author","Götz, Konrad R."],["dc.contributor.author","Nikolaev, Viacheslav O."],["dc.contributor.editor","Krieg, Thomas"],["dc.contributor.editor","Lukowski, Robert"],["dc.date.accessioned","2019-02-18T14:06:51Z"],["dc.date.available","2019-02-18T14:06:51Z"],["dc.date.issued","2013"],["dc.description.abstract","Förster resonance energy transfer (FRET)-based biosensors are powerful tools for real-time monitoring of signaling events in intact cells using fluorescence microscopy. Here, we describe a highly sensitive method which allows FRET-based measurements of the second messenger cGMP in adult mouse ventricular myocytes. Such measurements have been challenging before, primarily due to relatively low cGMP concentrations in cardiomyocytes and limited sensitivity of the available biosensors. With our new technique, one can reliably measure dynamic changes in cGMP upon stimulation of myocytes with natriuretic peptides and other physiological and pharmacological ligands."],["dc.identifier.doi","10.1007/978-1-62703-459-3_7"],["dc.identifier.pmid","23709029"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/57580"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/19"],["dc.language.iso","en"],["dc.notes.status","final"],["dc.publisher","Humana Press"],["dc.publisher.place","Totowa, NJ"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation","SFB 1002 | A01: cAMP- und cGMP- Mikrodomänen bei Herzhypertrophie und Insuffizienz"],["dc.relation.crisseries","Methods in Molecular Biology"],["dc.relation.doi","10.1007/978-1-62703-459-3"],["dc.relation.isbn","978-1-62703-458-6"],["dc.relation.isbn","978-1-62703-459-3"],["dc.relation.ispartof","Guanylate Cyclase and Cyclic GMP. Methods and Protocols"],["dc.relation.ispartofseries","Methods in Molecular Biology; 1020"],["dc.relation.issn","1064-3745"],["dc.relation.issn","1940-6029"],["dc.relation.workinggroup","RG Nikolaev (Cardiovascular Research Center)"],["dc.title","Advances and Techniques to Measure cGMP in Intact Cardiomyocytes"],["dc.type","book_chapter"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]