Würtz, Christina M.

[["dc.bibliographiccitation.firstpage","165"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Journal of Molecular and Cellular Cardiology"],["dc.bibliographiccitation.lastpage","175"],["dc.bibliographiccitation.volume","53"],["dc.contributor.author","Vettel, Christiane"],["dc.contributor.author","Wittig, Karola"],["dc.contributor.author","Vogt, Andreas"],["dc.contributor.author","Wuertz, Christina M."],["dc.contributor.author","El-Armouche, Ali"],["dc.contributor.author","Lutz, Susanne"],["dc.contributor.author","Wieland, Thomas"],["dc.date.accessioned","2018-11-07T09:07:59Z"],["dc.date.available","2018-11-07T09:07:59Z"],["dc.date.issued","2012"],["dc.description.abstract","Activation of alpha(1)-adrenoceptors (alpha(1)-AR) by high catecholamine levels, e.g. in heart failure, is thought to be a driving force of cardiac hypertrophy. In this context several downstream mediators and cascades have been identified to potentially play a role in cardiomyocyte hypertrophy. One of these proteins is the monomeric G protein Rac1. However, until now it is unclear how this essential G protein is activated by alpha(1)-AR agonists and what are the downstream targets inducing cellular growth. By using protein-based as well as pharmacological inhibitors and the shRNA technique, we demonstrate that in neonatal rat cardiomyocytes (NRCM) Rac1 is activated via a cascade involving the alpha(1A)-AR subtype, G(i)beta gamma, the phosphoinositide-3'-kinase and the guanine nucleotide exchange factor Tiam1. We further demonstrate that this signaling induces an increase in protein synthesis, cell size and atrial natriuretic peptide expression. We identified the p21-activated kinase 2 (PAK2) as a downstream effector of Rac1 and were able to link this cascade to the activation of the pro-hypertrophic kinases ERK1/2 and p90RSK. Our data thus reveal a prominent role of the alpha(1A)-AR/G(i)beta gamma/Tiam1-mediated activation of Rac1 and its effector PAK2 in the induction of hypertrophy in NRCM. (C) 2012 Elsevier Ltd. All rights reserved."],["dc.identifier.doi","10.1016/j.yjmcc.2012.04.015"],["dc.identifier.isi","000306451600003"],["dc.identifier.pmid","22564263"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/25922"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Academic Press Ltd- Elsevier Science Ltd"],["dc.relation.issn","1095-8584"],["dc.relation.issn","0022-2828"],["dc.title","A novel player in cellular hypertrophy: G(i)beta gamma/PI3K-dependent activation of the RacGEF TIAM-1 is required for alpha(1)-adrenoceptor induced hypertrophy in neonatal rat cardiomyocytes"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","39"],["dc.bibliographiccitation.journal","Journal of Molecular and Cellular Cardiology"],["dc.bibliographiccitation.lastpage","54"],["dc.bibliographiccitation.volume","88"],["dc.contributor.author","Ongherth, Anita"],["dc.contributor.author","Pasch, Sebastian"],["dc.contributor.author","Wuertz, Christina M."],["dc.contributor.author","Nowak, Karolin"],["dc.contributor.author","Kittana, Naim"],["dc.contributor.author","Weis, Cleo A."],["dc.contributor.author","Jatho, Aline"],["dc.contributor.author","Vettel, Christiane"],["dc.contributor.author","Tiburcy, Malte"],["dc.contributor.author","Toischer, Karl"],["dc.contributor.author","Hasenfuß, Gerd"],["dc.contributor.author","Zimmermann, Wolfram-Hubertus"],["dc.contributor.author","Wieland, Thomas"],["dc.contributor.author","Lutz, Susanne"],["dc.date.accessioned","2017-09-07T11:43:27Z"],["dc.date.available","2017-09-07T11:43:27Z"],["dc.date.issued","2015"],["dc.description.abstract","Cardiac remodeling, a hallmark of heart disease, is associated with intense auto- and paracrine signaling leading to cardiac fibrosis. We hypothesized that the specific mediator of G(q/11)-dependent RhoA activation p63RhoGEF, which is expressed in cardiac fibroblasts, plays a role in the underlying processes. We could show that p63RhoGEF is up-regulated in mouse hearts subjected to transverse aortic constriction (TAC). In an engineered heart muscle model (EHM), p63RhoGEF expression in cardiac fibroblasts increased resting and twitch tensions, and the dominant negative p63 Delta N decreased both. In an engineered connective tissue model (ECT), p63RhoGEF increased tissue stiffness and its knockdown as well as p63 Delta N reduced stiffness. In 2D cultures of neonatal rat cardiac fibroblasts, p63RhoGEF regulated the angiotensin II (Ang II)-dependent RhoA activation, the activation of the serum response factor, and the expression and secretion of the connective tissue growth factor (CTGF). All these processes were inhibited by the knockdown of p63RhoGEF or by p63 Delta N likely based on their negative influence on the actin cytoskeleton. Moreover, we show that p63RhoGEF also regulates CTGF in engineered tissues and correlates with it in the TAC model. Finally, confocal studies revealed a closely related localization of p63RhoGEF and CTGF in the trans-Golgi network. (C) 2015 Published by Elsevier Ltd."],["dc.identifier.doi","10.1016/j.yjmcc.2015.09.009"],["dc.identifier.gro","3141795"],["dc.identifier.isi","000365059300004"],["dc.identifier.pmid","26392029"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/1157"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/117"],["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 | C02: RhoGTPasen und ihre Bedeutung für die Last-abhängige Myokardfibrose"],["dc.relation","SFB 1002 | C04: Fibroblasten-Kardiomyozyten Interaktion im gesunden und erkrankten Herzen: Mechanismen und therapeutische Interventionen bei Kardiofibroblastopathien"],["dc.relation.eissn","1095-8584"],["dc.relation.issn","0022-2828"],["dc.relation.workinggroup","RG Hasenfuß (Transition zur Herzinsuffizienz)"],["dc.relation.workinggroup","RG Lutz (G Protein-Coupled Receptor Mediated Signaling)"],["dc.relation.workinggroup","RG Tiburcy (Stem Cell Disease Modeling)"],["dc.relation.workinggroup","RG Toischer (Kardiales Remodeling)"],["dc.relation.workinggroup","RG Zimmermann (Engineered Human Myocardium)"],["dc.title","p63RhoGEF regulates auto- and paracrine signaling in cardiac fibroblasts"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","4865"],["dc.bibliographiccitation.issue","12"],["dc.bibliographiccitation.journal","The FASEB Journal"],["dc.bibliographiccitation.lastpage","4876"],["dc.bibliographiccitation.volume","24"],["dc.contributor.author","Wuertz, Christina M."],["dc.contributor.author","Lorincz, Akos"],["dc.contributor.author","Vettel, Christiane"],["dc.contributor.author","Thomas, Martin A."],["dc.contributor.author","Wieland, Thomas"],["dc.contributor.author","Lutz, Susanne"],["dc.date.accessioned","2018-11-07T08:36:13Z"],["dc.date.available","2018-11-07T08:36:13Z"],["dc.date.issued","2010"],["dc.description.abstract","The purpose of our study was to investigate the role of endogenous p63RhoGEF in G(q/11)-dependent RhoA activation and signaling in rat aortic smooth muscle cells (RASMCs). Therefore, we studied the expression and subcellular localization in freshly isolated RASMCs and performed loss of function experiments to analyze its contribution to RhoGTPase activation and functional responses such as proliferation and contraction. By this, we could show that p63RhoGEF is endogenously expressed in RASMCs and acts there as the dominant mediator of the fast angiotensin II (ANG II)-dependent but not of the sphingosine-1-phosphate (S1P)-dependent RhoA activation. p63RhoGEF is not an activator of the concomitant Rac1 activation and functions independently of caveolae. The knockdown of endogenous p63RhoGEF significantly reduced the mitogenic response of ANG II, abolished ANG II-induced stress fiber formation and cell elongation in 2-D culture, and impaired the ANG II-driven contraction in a collagen-based 3-D model. In conclusion, our data provide for the first time evidence that p63RhoGEF is an important mediator of ANG II-dependent RhoA activation in RASMCs and therewith a leading actor in the subsequently triggered cellular processes, such as proliferation and contraction.-Wuertz, C. M., Lorincz, A., Vettel, C., Thomas, M. A., Wieland, T., Lutz, S. p63RhoGEF-a key mediator of angiotensin II-dependent signaling and processes in vascular smooth muscle cells. FASEB J. 24, 4865-4876 (2010). www.fasebj.org"],["dc.description.sponsorship","Deutsche Forschungsgemeinschaft [Lu1486/1-1, SFB TR 23 TP B6]"],["dc.identifier.doi","10.1096/fj.10-155499"],["dc.identifier.isi","000284824400026"],["dc.identifier.pmid","20739613"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/6271"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/18258"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Federation Amer Soc Exp Biol"],["dc.relation.issn","0892-6638"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","p63RhoGEF-a key mediator of angiotensin II-dependent signaling and processes in vascular smooth muscle cells"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","European Journal of Heart Failure"],["dc.bibliographiccitation.volume","12"],["dc.contributor.author","Vettel, Christiane"],["dc.contributor.author","Laemmle, Simon"],["dc.contributor.author","Emons, J."],["dc.contributor.author","Ewens, S."],["dc.contributor.author","Cervirgen, C."],["dc.contributor.author","Wittkoepper, Katrin"],["dc.contributor.author","Wuertz, Christina M."],["dc.contributor.author","Lutz, S."],["dc.contributor.author","Zimmermann, Wolfram-Hubertus"],["dc.contributor.author","El-Armouche, Ali"],["dc.date.accessioned","2018-11-07T09:25:44Z"],["dc.date.available","2018-11-07T09:25:44Z"],["dc.date.issued","2013"],["dc.format.extent","S64"],["dc.identifier.isi","000332489100238"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/30137"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-blackwell"],["dc.publisher.place","Hoboken"],["dc.relation.issn","1879-0844"],["dc.relation.issn","1388-9842"],["dc.title","Phosphodiesterase 2 activates myofibroblast formation and CTGF synthesis in cardiac fibroblasts and augments stiffness in engineered connective tissue"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Naunyn-Schmiedeberg s Archives of Pharmacology"],["dc.bibliographiccitation.volume","383"],["dc.contributor.author","Wuertz, Christina"],["dc.contributor.author","Weis, C.-A."],["dc.contributor.author","Vettel, Christiane"],["dc.contributor.author","Nowak, K."],["dc.contributor.author","Otte, K."],["dc.contributor.author","Ewens, S."],["dc.contributor.author","Tiburcy, Malte"],["dc.contributor.author","Schubert, P."],["dc.contributor.author","Zimmermann, Wolfram-Hubertus"],["dc.contributor.author","Wieland, Thomas"],["dc.contributor.author","Lutz, S."],["dc.date.accessioned","2018-11-07T08:58:30Z"],["dc.date.available","2018-11-07T08:58:30Z"],["dc.date.issued","2011"],["dc.format.extent","11"],["dc.identifier.isi","000288573100043"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/23655"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Springer"],["dc.publisher.place","New york"],["dc.relation.eventlocation","Frankfurt, GERMANY"],["dc.relation.issn","0028-1298"],["dc.title","The expression and secretion of the connective tissue growth factor in cardiac fibroblasts is controlled through the RhoA signaling axis"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["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"]]

[["dc.bibliographiccitation.journal","Naunyn-Schmiedeberg s Archives of Pharmacology"],["dc.bibliographiccitation.volume","383"],["dc.contributor.author","Weis, C.-A."],["dc.contributor.author","Vettel, Christiane"],["dc.contributor.author","Wuertz, Christina"],["dc.contributor.author","Wieland, Thomas"],["dc.contributor.author","Lutz, S."],["dc.date.accessioned","2018-11-07T08:58:33Z"],["dc.date.available","2018-11-07T08:58:33Z"],["dc.date.issued","2011"],["dc.format.extent","64"],["dc.identifier.isi","000288573100318"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/23667"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Springer"],["dc.publisher.place","New york"],["dc.relation.conference","77th Annual Meeting on German-Society-for-Experimental-and-Clinical-Pharmacology-and-Toxicology"],["dc.relation.eventlocation","Frankfurt, GERMANY"],["dc.relation.issn","0028-1298"],["dc.title","Angiotensin II-induces activation of RhoA via an AT(1)R-, G(q/11)- and p63RhoGEF-dependent pathway in caveolae of neonatal cardiac fibroblasts"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]