Wagner, Stefan

[["dc.bibliographiccitation.issue","8"],["dc.bibliographiccitation.journal","Insects"],["dc.bibliographiccitation.volume","13"],["dc.contributor.affiliation","Stein, Frederik; 1Institute for Plant Protection in Horticulture and Forests, Julius Kühn Institute, 38014 Braunschweig, Germany; stefan.wagner@julius-kuehn.de (S.W.); nadine.braesicke@julius-kuehn.de (N.B.); monika.goetz@julius-kuehn.de (M.G.)"],["dc.contributor.affiliation","Wagner, Stefan; 1Institute for Plant Protection in Horticulture and Forests, Julius Kühn Institute, 38014 Braunschweig, Germany; stefan.wagner@julius-kuehn.de (S.W.); nadine.braesicke@julius-kuehn.de (N.B.); monika.goetz@julius-kuehn.de (M.G.)"],["dc.contributor.affiliation","Bräsicke, Nadine; 1Institute for Plant Protection in Horticulture and Forests, Julius Kühn Institute, 38014 Braunschweig, Germany; stefan.wagner@julius-kuehn.de (S.W.); nadine.braesicke@julius-kuehn.de (N.B.); monika.goetz@julius-kuehn.de (M.G.)"],["dc.contributor.affiliation","Gailing, Oliver; 2Büsgen Institute, Forest Genetics and Forest Tree Breeding, University of Göttingen, 37073 Göttingen, Germany; ogailin@gwdg.de (O.G.); carinamoura@uni-goettingen.de (C.C.M.M.)"],["dc.contributor.affiliation","Moura, Carina C. M.; 2Büsgen Institute, Forest Genetics and Forest Tree Breeding, University of Göttingen, 37073 Göttingen, Germany; ogailin@gwdg.de (O.G.); carinamoura@uni-goettingen.de (C.C.M.M.)"],["dc.contributor.affiliation","Götz, Monika; 1Institute for Plant Protection in Horticulture and Forests, Julius Kühn Institute, 38014 Braunschweig, Germany; stefan.wagner@julius-kuehn.de (S.W.); nadine.braesicke@julius-kuehn.de (N.B.); monika.goetz@julius-kuehn.de (M.G.)"],["dc.contributor.author","Stein, Frederik"],["dc.contributor.author","Wagner, Stefan"],["dc.contributor.author","Bräsicke, Nadine"],["dc.contributor.author","Gailing, Oliver"],["dc.contributor.author","Moura, Carina C. M."],["dc.contributor.author","Götz, Monika"],["dc.date.accessioned","2022-08-03T14:37:47Z"],["dc.date.available","2022-08-03T14:37:47Z"],["dc.date.issued","2022-07-27"],["dc.date.updated","2022-08-03T13:13:47Z"],["dc.description.abstract","Molecular genetic identification of insect species usually requires destructive DNA isolation for insects. Due to database gaps, errors, or low resolution of the examined gene region, a supplementary morphological identification may be necessary. To employ taxonomical experts efficiently, we developed a fast, economic, and simple non-destructive way for the molecular genetic species identification of flies and other soft-bodied insects.\r\n \r\n \r\n Abstract\r\n While the need for biodiversity research is growing, paradoxically, global taxonomical expertise is decreasing as a result of the neglected funding for young academics in taxonomy. Non-destructive approaches for DNA barcoding are necessary for a more efficient use of this dwindling expertise to fill gaps, and identify incorrect entries in sequence databases like BOLD or GenBank. They are efficient because morphological re-examination of species vouchers is still possible post-DNA barcoding. Non-destructive approaches for Diptera with a comprehensive species representation or the consideration of diagnostic fragile morphological characters are missing. Additionally, most non-destructive approaches combine a time intensive and non-destructive digestion step with common DNA extraction methods, such as commercial kits or CTAB DNA isolation. We circumvented those approaches and combined a modified non-destructive TE buffer high-speed DNA extraction, with a PCR inhibitor-resistant PCR reaction system, to a non-destructive DNA barcoding procedure for fresh and frozen samples of the Schizophora (Diptera). This method avoids morphological impairment and the application of harmful chemicals, is cost and time effective, restricts the need for laboratory equipment to a minimum, and prevents cross-contamination risk during DNA isolation. Moreover, the study indicates that the presented non-destructive DNA barcoding procedure is transferable to other soft-bodied insects. We suggest that PCR inhibitor-resistant master mixes enable the development of new—and the modification of existing—non-destructive approaches with the avoidance of further DNA template cleaning."],["dc.description.sponsorship","Fachagentur für Nachwachsende Rohstoffe"],["dc.identifier.doi","10.3390/insects13080679"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/112608"],["dc.language.iso","en"],["dc.relation.eissn","2075-4450"],["dc.rights","CC BY 4.0"],["dc.title","A Non-Destructive High-Speed Procedure to Obtain DNA Barcodes from Soft-Bodied Insect Samples with a Focus on the Dipteran Section of Schizophora"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","263"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Basic Research in Cardiology"],["dc.bibliographiccitation.lastpage","272"],["dc.bibliographiccitation.volume","106"],["dc.contributor.author","Sossalla, Samuel"],["dc.contributor.author","Maurer, Ulrike"],["dc.contributor.author","Schotola, Hanna"],["dc.contributor.author","Hartmann, Nico H."],["dc.contributor.author","Didie, Michael"],["dc.contributor.author","Zimmermann, Wolfram-Hubertus"],["dc.contributor.author","Jacobshagen, Claudius"],["dc.contributor.author","Wagner, Stefan"],["dc.contributor.author","Maier, Lars S."],["dc.date.accessioned","2017-09-07T11:44:20Z"],["dc.date.available","2017-09-07T11:44:20Z"],["dc.date.issued","2011"],["dc.description.abstract","Transgenic (TG) Ca2+/calmodulin-dependent protein kinase II (CaMKII) delta(C) mice develop systolic heart failure (HF). CaMKII regulates intracellular Ca2+ handling proteins as well as sarcolemmal Na+ channels. We hypothesized that CaMKII also contributes to diastolic dysfunction and arrhythmias via augmentation of the late Na+ current (late I (Na)) in early HF (8-week-old TG mice). Echocardiography revealed severe diastolic dysfunction in addition to decreased systolic ejection fraction. Premature arrhythmogenic contractions (PACs) in isolated isometrically twitching papillary muscles only occurred in TG preparations (5 vs. 0, P < 0.05) which could be completely terminated when treated with the late I (Na) inhibitor ranolazine (Ran, 5 mu mol/L). Force-frequency relationships revealed significantly reduced twitch force amplitudes in TG papillary muscles. Most importantly, diastolic tension increased with raising frequencies to a greater extent in TG papillary muscles compared to WT specimen (at 10 Hz: 3.7 +/- A 0.4 vs. 2.5 +/- A 0.3 mN/mm(2); P < 0.05). Addition of Ran improved diastolic dysfunction to 2.1 +/- A 0.2 mN/mm(2) (at 10 Hz; P < 0.05) without negative inotropic effects. Mechanistically, the late I (Na) was markedly elevated in myocytes isolated from TG mice and could be completely reversed by Ran. In conclusion, our results show for the first time that TG CaMKII delta(C) overexpression induces diastolic dysfunction and arrhythmogenic triggers possibly via an enhanced late I (Na). Inhibition of elevated late I (Na) had beneficial effects on arrhythmias as well as diastolic function in papillary muscles from CaMKII delta(C) TG mice. Thus, late I (Na) inhibition appears to be a promising option for diastolic dysfunction and arrhythmias in HF where CaMKII is found to be increased."],["dc.identifier.doi","10.1007/s00395-010-0136-x"],["dc.identifier.gro","3142765"],["dc.identifier.isi","000286934300008"],["dc.identifier.pmid","21174213"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/7315"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/205"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Springer"],["dc.publisher.place","Heidelberg"],["dc.relation.issn","0300-8428"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Diastolic dysfunction and arrhythmias caused by overexpression of CaMKII delta(C) can be reversed by inhibition of late Na+ current"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","726"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Diabetologia"],["dc.bibliographiccitation.lastpage","729"],["dc.bibliographiccitation.volume","62"],["dc.contributor.author","Mustroph, Julian"],["dc.contributor.author","Lücht, Charlotte M."],["dc.contributor.author","Wagemann, Olivia"],["dc.contributor.author","Sowa, Thomas"],["dc.contributor.author","Hammer, Karin P."],["dc.contributor.author","Sag, Can M."],["dc.contributor.author","Tarnowski, Daniel"],["dc.contributor.author","Holzamer, Andreas"],["dc.contributor.author","Pabel, Steffen"],["dc.contributor.author","Beuthner, Bo Eric"],["dc.contributor.author","Sossalla, Samuel"],["dc.contributor.author","Maier, Lars S."],["dc.contributor.author","Wagner, Stefan"],["dc.date.accessioned","2019-07-09T11:51:32Z"],["dc.date.available","2019-07-09T11:51:32Z"],["dc.date.issued","2019"],["dc.identifier.doi","10.1007/s00125-019-4819-z"],["dc.identifier.pmid","30694352"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/16145"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59964"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject.ddc","610"],["dc.title","Empagliflozin enhances human and murine cardiomyocyte glucose uptake by increased expression of GLUT1"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","555"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Circulation Research"],["dc.bibliographiccitation.lastpage","565"],["dc.bibliographiccitation.volume","108"],["dc.contributor.author","Wagner, Stefan"],["dc.contributor.author","Ruff, Hanna M."],["dc.contributor.author","Weber, Sarah L."],["dc.contributor.author","Bellmann, Sarah"],["dc.contributor.author","Sowa, Thomas"],["dc.contributor.author","Schulte, Timo"],["dc.contributor.author","Anderson, Mark E."],["dc.contributor.author","Grandi, Eleonora"],["dc.contributor.author","Bers, Donald M."],["dc.contributor.author","Backs, Johannes"],["dc.contributor.author","Belardinelli, Luiz"],["dc.contributor.author","Maier, Lars. S."],["dc.date.accessioned","2018-11-07T08:58:14Z"],["dc.date.available","2018-11-07T08:58:14Z"],["dc.date.issued","2011"],["dc.description.abstract","Rationale: In heart failure, Ca/calmodulin kinase (CaMK) II expression and reactive oxygen species (ROS) are increased. Both ROS and CaMKII can increase late I-Na leading to intracellular Na accumulation and arrhythmias. It has been shown that ROS can activate CaMKII via oxidation. Objective: We tested whether CaMKII delta is required for ROS-dependent late I-Na regulation and whether ROS-induced Ca released from the sarcoplasmic reticulum (SR) is involved. Methods and Results: 40 mu mol/L H2O2 significantly increased CaMKII oxidation and autophosphorylation in permeabilized rabbit cardiomyocytes. Without free [Ca](i) (5 mmol/L BAPTA/1 mmol/L Br-2-BAPTA) or after SR depletion (caffeine 10 mmol/L, thapsigargin 5 mu mol/L), the H2O2-dependent CaMKII oxidation and autophosphorylation was abolished. H2O2 significantly increased SR Ca spark frequency (confocal microscopy) but reduced SR Ca load. In wild-type (WT) mouse myocytes, H2O2 increased late I-Na (whole cell patch-clamp). This increase was abolished in CaMKII delta(-/-) myocytes. H2O2-induced [Na](i) and [Ca](i) accumulation (SBFI [sodium-binding benzofuran isophthalate] and Indo-1 epifluorescence) was significantly slowed in CaMKII delta(-/-) myocytes (versus WT). CaMKII delta(-/-) myocytes developed significantly less H2O2-induced arrhythmias and were more resistant to hypercontracture. Opposite results (increased late I-Na, [Na](i) and [Ca](i) accumulation) were obtained by overexpression of CaMKII delta in rabbit myocytes (adenoviral gene transfer) reversible with CaMKII inhibition (10 mu mol/L KN93 or 0.1 mu mol/L AIP [autocamtide 2-related inhibitory peptide]). Conclusions: Free [Ca](i) and a functional SR are required for ROS activation of CaMKII. ROS-activated CaMKII delta enhances late I-Na, which may lead to cellular Na and Ca overload. This may be of relevance in hear failure, where enhanced ROS production meets increased CaMKII expression. (Circ Res. 2011; 108: 555-565.)"],["dc.identifier.doi","10.1161/CIRCRESAHA.110.221911"],["dc.identifier.isi","000287963900009"],["dc.identifier.pmid","21252154"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/7822"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/23593"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Lippincott Williams & Wilkins"],["dc.relation.issn","0009-7330"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Reactive Oxygen Species-Activated Ca/Calmodulin Kinase II delta Is Required for Late I-Na Augmentation Leading to Cellular Na and Ca Overload"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","20"],["dc.bibliographiccitation.journal","Frontiers in Pharmacology"],["dc.bibliographiccitation.volume","5"],["dc.contributor.author","Mustroph, Julian"],["dc.contributor.author","Maier, Lars S."],["dc.contributor.author","Wagner, Stefan"],["dc.date.accessioned","2018-11-07T09:43:39Z"],["dc.date.available","2018-11-07T09:43:39Z"],["dc.date.issued","2014"],["dc.description.abstract","Cardiac K channels are critical determinants of cardiac excitability. In hypertrophied and failing myocardium, alterations in the expression and activity of voltage-gated K channels are frequently observed and contribute to the increased propensity for life-threatening arrhythmias. Thus, understanding the mechanisms of disturbed K channel regulation in heart failure (HF) is of critical importance. Amongst others, Ca/calmodulin-dependent protein kinase II (CaMKII) has been identified as an important regulator of K channel activity. In human HF but also various animal models, increased CaMKI I expression and activity has been linked to deteriorated contractile function and arrhythmias. This review will discuss the current knowledge about CaMKII regulation of several K channels, its influence on action potential properties, dispersion of repolanzation, and arrhythmias with special focus on HF"],["dc.description.sponsorship","Open-Access-Publikationsfonds 2014"],["dc.identifier.doi","10.3389/fphar.2014.00020"],["dc.identifier.isi","000347047500001"],["dc.identifier.pmid","24600393"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/9943"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/34226"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/39"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation","SFB 1002 | A03: Bedeutung CaMKII-abhängiger Mechanismen für die Arrhythmogenese bei Herzinsuffizienz"],["dc.relation.eissn","1663-9812"],["dc.relation.issn","1663-9812"],["dc.relation.workinggroup","RG L. Maier (Experimentelle Kardiologie)"],["dc.rights","CC BY 3.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/3.0"],["dc.title","CaMKII regulation of cardiac K channels"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","overview_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","2330"],["dc.bibliographiccitation.issue","21"],["dc.bibliographiccitation.journal","Journal of the American College of Cardiology"],["dc.bibliographiccitation.lastpage","2342"],["dc.bibliographiccitation.volume","55"],["dc.contributor.author","Sossalla, Samuel"],["dc.contributor.author","Kallmeyer, Birte"],["dc.contributor.author","Wagner, Stefan"],["dc.contributor.author","Mazur, Marek"],["dc.contributor.author","Maurer, Ulrike"],["dc.contributor.author","Toischer, Karl"],["dc.contributor.author","Schmitto, Jan D."],["dc.contributor.author","Seipelt, Ralf"],["dc.contributor.author","Schoendube, Friedrich A."],["dc.contributor.author","Hasenfuß, Gerd"],["dc.contributor.author","Belardinelli, Luiz"],["dc.contributor.author","Maier, Lars S."],["dc.date.accessioned","2017-09-07T11:46:03Z"],["dc.date.available","2017-09-07T11:46:03Z"],["dc.date.issued","2010"],["dc.description.abstract","Objectives We investigated changes in Na+ currents (I-Na) in permanent (or chronic) atrial fibrillation (AF) and the effects of I-Na inhibition using ranolazine (Ran) on arrhythmias and contractility in human atrial myocardium. Background Electrical remodeling during AF is typically associated with alterations in Ca2+ and K+ currents. It remains unclear whether I-Na is also altered. Methods Right atrial appendages from patients with AF (n = 23) and in sinus rhythm (SR) (n = 79) were studied. Results Patch-clamp experiments in isolated atrial myocytes showed significantly reduced peak I-Na density (similar to 16%) in AF compared with SR, which was accompanied by a 26% lower expression of Nav1.5 (p < 0.05). In contrast, late I-Na was significantly increased in myocytes from AF atria by similar to 26%. Ran (10 mu mol/l) decreased late I-Na by similar to 60% (p < 0.05) in myocytes from patients with AF but only by similar to 18% (p < 0.05) in myocytes from SR atria. Proarrhythmic activity was elicited in atrial trabeculae exposed to high [Ca2+](o) or isoprenaline, which was significantly reversed by Ran (by 83% and 100%, respectively). Increasing pacing rates from 0.5 to 3.0 Hz led to an increase in diastolic tension that could be significantly decreased by Ran in atria from SR and AF patients. Conclusions Na+ channels may contribute to arrhythmias and contractile remodeling in AF. Inhibition of I-Na with Ran had antiarrhythmic effects and improved diastolic function. Thus, inhibition of late I-Na may be a promising new treatment option for patients with atrial rhythm disturbances and diastolic dysfunction. (J Am Coll Cardiol 2010;55:2330-42) (C) 2010 by the American College of Cardiology Foundation"],["dc.identifier.doi","10.1016/j.jacc.2009.12.055"],["dc.identifier.gro","3142922"],["dc.identifier.isi","000277805800007"],["dc.identifier.pmid","20488304"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/6156"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/379"],["dc.notes.intern","WoS Import 2017-03-10 / Funder: DFG [MA1982/4-1]; Klinische Forschergruppe [MA1982/2-2]; CV Therapeutics"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Elsevier Science Inc"],["dc.relation.issn","0735-1097"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Altered Na+ Currents in Atrial Fibrillation Effects of Ranolazine on Arrhythmias and Contractility in Human Atrial Myocardium"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.seriesnr","5"],["dc.contributor.author","Ammer, Christian"],["dc.contributor.author","Vor, Torsten"],["dc.contributor.author","Knoke, Thomas"],["dc.contributor.author","Wagner, Stefan"],["dc.date.accessioned","2018-01-02T12:29:25Z"],["dc.date.available","2018-01-02T12:29:25Z"],["dc.date.issued","2010"],["dc.description.abstract","Die ökologischen und ökonomischen Risiken, die sich aus der in Deutschland üblichen Schalenwildbewirtschaftung für Waldökosysteme ergeben, werden allgemein unterschätzt. Die vor allem durch Wildverbiss verursachten Schäden verringern die Schutzwirkung von Wäldern und beeinträchtigen den vor dem Hintergrund des Klimawandels notwendigen Waldumbau. Die gesetzlichen Grundlagen für eine Verbesserung der Situation sind größtenteils bereits vorhanden, in einigen entscheidenden Punkten jedoch verbesserungsbedürftig. Es fehlt aber an deren Umsetzung. Es werden Möglichkeiten aufgezeigt, die Probleme zwischen der forstlichen Haupt- und der jagdlichen Nebennutzung zu lösen oder zumindest zu entschärfen. Das in dem Band diskutierte Instrumentarium reicht von der Stärkung des Verantwortungsbewusstseins aller Akteure bis hin zu denkbaren Sanktionen bei gleichbleibenden Verbissschäden."],["dc.format.extent","184"],["dc.identifier.doi","10.17875/gup2010-280"],["dc.identifier.isbn","978-3-941875-84-5"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/6354"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/11526"],["dc.language.iso","de"],["dc.notes.intern","Migrated from goescholar"],["dc.notes.status","final"],["dc.publisher","Universitätsverlag Göttingen"],["dc.publisher.place","Göttingen"],["dc.relation.crisseries","Göttinger Forstwissenschaften"],["dc.relation.ispartofseries","Göttinger Forstwissenschaften; 5"],["dc.rights","CC BY-ND 3.0"],["dc.rights.access","openAccess"],["dc.rights.uri","https://creativecommons.org/licenses/by-nd/2.0"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.subject","OAPEN"],["dc.subject.ddc","570"],["dc.title","Der Wald-Wild-Konflikt. Analyse und Lösungsansätze vor dem Hintergrund rechtlicher, ökologischer und ökonomischer Zusammenhänge"],["dc.type","book"],["dc.type.internalPublication","unknown"],["dc.type.peerReviewed","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","33"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Journal of Molecular and Cellular Cardiology"],["dc.bibliographiccitation.lastpage","42"],["dc.bibliographiccitation.volume","50"],["dc.contributor.author","Seidler, Tim"],["dc.contributor.author","Teucher, Nils"],["dc.contributor.author","Hellenkamp, Kristian"],["dc.contributor.author","Unsoeld, Bernhard W."],["dc.contributor.author","Grebe, Cornelia"],["dc.contributor.author","Kramps, Petra"],["dc.contributor.author","Schotola, Hanna"],["dc.contributor.author","Wagner, Stefan"],["dc.contributor.author","Schoendube, Friedrich A."],["dc.contributor.author","Hasenfuß, Gerd"],["dc.contributor.author","Maier, Lars S."],["dc.date.accessioned","2017-09-07T11:45:07Z"],["dc.date.available","2017-09-07T11:45:07Z"],["dc.date.issued","2011"],["dc.description.abstract","Sarcoplasmic reticulum (SR) calcium (Ca) leak can be reduced by enhancing FKBP12.6 binding to SR Ca release channels (RyR2) and expression of a \"sticky\" FKBP12.6(D37s) mutant may correct reduced binding stoichiometry in RyR2 from failing hearts. Both calcium/calmodulin-dependent protein kinase II delta c (CaMKII delta c) and protein kinase A (PKA) are activated in heart failure and promote SR Ca leak at RyR2. It is possible that FKBP12.6 dissociation from RyR2 may promote remodeling and that interventions to reassociate FKBP12.6 with RyR2 reflect a future therapeutic strategy. We created transgenic (TG) mice expressing FKBP12.6(D37s) and tested their capacity to improve intracellular Ca handling and pathological remodeling in vivo. FKBP12.6(D37S) TG mice were cross-bred with CaMKII delta c TG mice, which are known to exhibit pronounced RyR2 dysfunction and heart failure. We observed a significant improvement of post-rest Ca transients and a higher SR Ca content in FKBP12.6(D37S) TG mice. In double-TG mice, a marked reduction of SR Ca spark frequency indicated reduced SR Ca leak but neither SR Ca transient amplitude, SR Ca content nor morphological or functional parameters improved in vivo. Likewise, FKBP12.6(D37s) TG mice subjected to increased afterload after aortic banding exhibited higher SR Ca load but did not exhibit any improvement in hypertrophic growth or functional decline. Enhancement of FKBP12.6-RyR2 binding markedly reduced RyR2 Ca leak in CaMKII delta c-induced heart failure and in pressure overload. Our data suggest that activation of CaMKII delta c and pressure overload confer significant resistance towards approaches aiming at FKBP12.6-RyR2 reconstitution in heart failure and maladaptive remodeling, although RyR2 Ca leak can be reduced. (C) 2010 Elsevier Ltd. All rights reserved."],["dc.identifier.doi","10.1016/j.yjmcc.2010.08.016"],["dc.identifier.gro","3142803"],["dc.identifier.isi","000286502800008"],["dc.identifier.pmid","20797399"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/6309"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/248"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Academic Press Ltd- Elsevier Science Ltd"],["dc.relation.eissn","1095-8584"],["dc.relation.issn","0022-2828"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Limitations of FKBP12.6-directed treatment strategies for maladaptive cardiac remodeling and heart failure"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","33853"],["dc.bibliographiccitation.journal","Scientific Reports"],["dc.bibliographiccitation.volume","6"],["dc.contributor.author","Volland, Cornelia"],["dc.contributor.author","Bremer, Sebastian"],["dc.contributor.author","Hellenkamp, Kristian"],["dc.contributor.author","Hartmann, Nico H."],["dc.contributor.author","Dybkova, Nataliya"],["dc.contributor.author","Khadjeh, Sara"],["dc.contributor.author","Kutschenko, Anna"],["dc.contributor.author","Liebetanz, David"],["dc.contributor.author","Wagner, Stefan"],["dc.contributor.author","Unsoeld, Bernhard W."],["dc.contributor.author","Didie, Michael"],["dc.contributor.author","Toischer, Karl"],["dc.contributor.author","Sossalla, Samuel"],["dc.contributor.author","Hasenfuß, Gerd"],["dc.contributor.author","Seidler, Tim"],["dc.date.accessioned","2017-09-07T11:44:37Z"],["dc.date.available","2017-09-07T11:44:37Z"],["dc.date.issued","2016"],["dc.description.abstract","TBC1D10C is a protein previously demonstrated to bind and inhibit Ras and Calcineurin. In cardiomyocytes, also CaMKII is inhibited and all three targeted enzymes are known to promote maladaptive cardiomyocyte hypertrophy. Here, in accordance with lack of Calcineurin inhibition in vivo, we did not observe a relevant anti-hypertrophic effect despite inhibition of Ras and CaMKII. However, cardiomyocyte-specific TBC1D10C overexpressing transgenic mice exhibited enhanced longevity. Ejection fraction and exercise capacity were enhanced in transgenic mice, but shortening of isolated cardiomyocytes was not increased. This suggests longevity resulted from enhanced cardiac performance but independent of cardiomyocyte contractile force. In further search for mechanisms, a transcriptome-wide analysis revealed expressional changes in several genes pertinent to control of heart rate (HR) including Hcn4, Scn10a, Sema3a and Cacna2d2. Indeed, telemetric holter recordings demonstrated slower atrial conduction and significantly lower HR. Pharmacological reduction of HR was previously demonstrated to enhance survival in mice. Thus, in addition to inhibition of stress signaling, TBC1D10C economizes generation of cardiac output via HR reduction, enhancing exercise capacity and survival. TBC1D10C may be a new target for HR reduction and longevity."],["dc.identifier.doi","10.1038/srep33853"],["dc.identifier.gro","3141617"],["dc.identifier.isi","000384478000002"],["dc.identifier.pmid","27667030"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/13792"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/1678"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Nature Publishing Group"],["dc.relation.issn","2045-2322"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Enhanced cardiac TBC1D10C expression lowers heart rate and enhances exercise capacity and survival"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]