Levent, Elif

[["dc.bibliographiccitation.journal","Frontiers in Physiology"],["dc.bibliographiccitation.volume","10"],["dc.contributor.author","Trautsch, Irina"],["dc.contributor.author","Heta, Eriona"],["dc.contributor.author","Soong, Poh Loong"],["dc.contributor.author","Levent, Elif"],["dc.contributor.author","Nikolaev, Viacheslav O."],["dc.contributor.author","Bogeski, Ivan"],["dc.contributor.author","Katschinski, Dörthe M."],["dc.contributor.author","Mayr, Manuel"],["dc.contributor.author","Zimmermann, Wolfram-Hubertus"],["dc.date.accessioned","2020-12-10T18:44:38Z"],["dc.date.available","2020-12-10T18:44:38Z"],["dc.date.issued","2019"],["dc.description.abstract","Redox signaling affects all aspects of cardiac function and homeostasis. With the development of genetically encoded fluorescent redox sensors, novel tools for the optogenetic investigation of redox signaling have emerged. Here, we sought to develop a human heart muscle model for in-tissue imaging of redox alterations. For this, we made use of (1) the genetically-encoded Grx1-roGFP2 sensor, which reports changes in cellular glutathione redox status (GSH/GSSG), (2) human embryonic stem cells (HES2), and (3) the engineered heart muscle (EHM) technology. We first generated HES2 lines expressing Grx1-roGFP2 in cytosol or mitochondria compartments by TALEN-guided genomic integration. Grx1-roGFP2 sensor localization and function was verified by fluorescence imaging. Grx1-roGFP2 HES2 were then subjected to directed differentiation to obtain high purity cardiomyocyte populations. Despite being able to report glutathione redox potential from cytosol and mitochondria, we observed dysfunctional sarcomerogenesis in Grx1-roGFP2 expressing cardiomyocytes. Conversely, lentiviral transduction of Grx1-roGFP2 in already differentiated HES2-cardiomyocytes and human foreskin fibroblast was possible, without compromising cell function as determined in EHM from defined Grx1-roGFP2-expressing cardiomyocyte and fibroblast populations. Finally, cell-type specific GSH/GSSG imaging was demonstrated in EHM. Collectively, our observations suggests a crucial role for redox signaling in cardiomyocyte differentiation and provide a solution as to how this apparent limitation can be overcome to enable cell-type specific GSH/GSSG imaging in a human heart muscle context."],["dc.identifier.doi","10.3389/fphys.2019.00272"],["dc.identifier.pmid","31024328"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/78535"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/265"],["dc.identifier.url","https://sfb1190.med.uni-goettingen.de/production/literature/publications/67"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation","SFB 1002 | C04: Fibroblasten-Kardiomyozyten Interaktion im gesunden und erkrankten Herzen: Mechanismen und therapeutische Interventionen bei Kardiofibroblastopathien"],["dc.relation","SFB 1002 | S01: In vivo und in vitro Krankheitsmodelle"],["dc.relation","SFB 1190: Transportmaschinen und Kontaktstellen zellulärer Kompartimente"],["dc.relation","SFB 1190 | P17: Die Rolle mitochondrialer Kontaktstellen im Rahmen tumorrelevanter Calcium- und Redox-Signalwege"],["dc.relation.eissn","1664-042X"],["dc.relation.workinggroup","RG Nikolaev (Cardiovascular Research Center)"],["dc.relation.workinggroup","RG Zimmermann (Engineered Human Myocardium)"],["dc.relation.workinggroup","RG Bogeski"],["dc.rights","http://creativecommons.org/licenses/by/4.0/"],["dc.title","Optogenetic Monitoring of the Glutathione Redox State in Engineered Human Myocardium"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","79"],["dc.bibliographiccitation.journal","Acta Physiologica"],["dc.bibliographiccitation.lastpage","80"],["dc.bibliographiccitation.volume","213"],["dc.contributor.author","Vogler, Melanie"],["dc.contributor.author","Zieseniss, Anke"],["dc.contributor.author","Hesse, Amke Rena"],["dc.contributor.author","Levent, Elif"],["dc.contributor.author","Tiburcy, Malte"],["dc.contributor.author","Heinze, Eva"],["dc.contributor.author","Burzlaff, Nicolai"],["dc.contributor.author","Schley, Gunnar"],["dc.contributor.author","Eckardt, K. U."],["dc.contributor.author","Willam, Carsten"],["dc.contributor.author","Katschinski, Doerthe Magdalena"],["dc.date.accessioned","2018-11-07T09:59:51Z"],["dc.date.available","2018-11-07T09:59:51Z"],["dc.date.issued","2015"],["dc.identifier.isi","000362554200170"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/37684"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-blackwell"],["dc.publisher.place","Hoboken"],["dc.relation.issn","1748-1716"],["dc.relation.issn","1748-1708"],["dc.title","Pre- and post-conditional inhibition of prolyl-4-hydroxylase domain enzymes protects the heart from an ischemic insult"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","2141"],["dc.bibliographiccitation.issue","10"],["dc.bibliographiccitation.journal","Pflügers Archiv - European Journal of Physiology"],["dc.bibliographiccitation.lastpage","2149"],["dc.bibliographiccitation.volume","467"],["dc.contributor.author","Vogler, Melanie"],["dc.contributor.author","Zieseniss, Anke"],["dc.contributor.author","Hesse, Amke Rena"],["dc.contributor.author","Levent, Elif"],["dc.contributor.author","Tiburcy, Malte"],["dc.contributor.author","Heinze, Eva"],["dc.contributor.author","Burzlaff, Nicolai"],["dc.contributor.author","Schley, Gunnar"],["dc.contributor.author","Eckardt, Kai Uwe"],["dc.contributor.author","Willam, Carsten"],["dc.contributor.author","Katschinski, Doerthe Magdalena"],["dc.date.accessioned","2018-11-07T09:51:21Z"],["dc.date.available","2018-11-07T09:51:21Z"],["dc.date.issued","2015"],["dc.description.abstract","Several genetically modified mouse models implicated that prolyl-4-hydroxylase domain (PHD) enzymes are critical mediators for protecting tissues from an ischemic insult including myocardial infarction by affecting the stability and activation of hypoxia-inducible factor (HIF)-1 and HIF-2. Thus, the current efforts to develop small-molecule PHD inhibitors open a new therapeutic option for myocardial tissue protection during ischemia. Therefore, we aimed to investigate the applicability and efficacy of pharmacological HIF alpha stabilization by a small-molecule PHD inhibitor in the heart. We tested for protective effects in the acute phase of myocardial infarction after pre- or post-conditional application of the inhibitor. Application of the specific PHD inhibitor 2-(1-chloro-4-hydroxyisoquinoline-3-carboxamido) acetate (ICA) resulted in HIF-1 alpha and HIF-2 alpha accumulation in heart muscle cells in vitro and in vivo. The rapid and robust responsiveness of cardiac tissue towards ICA was further confirmed by induction of the known HIF target genes heme oxygenase-1 and PHD3. Pre- and post-conditional treatment of mice undergoing myocardial infarction resulted in a significantly smaller infarct size. Tissue protection from ischemia after pre- or post-conditional ICA treatment demonstrates that there is a therapeutic time window for the application of the PHD inhibitor (PHI) post-myocardial infarction, which might be exploited for acute medical interventions."],["dc.identifier.doi","10.1007/s00424-014-1667-z"],["dc.identifier.isi","000361000800008"],["dc.identifier.pmid","25578858"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/35894"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Springer"],["dc.relation.issn","1432-2013"],["dc.relation.issn","0031-6768"],["dc.title","Pre- and post-conditional inhibition of prolyl-4-hydroxylase domain enzymes protects the heart from an ischemic insult"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1694"],["dc.bibliographiccitation.issue","17"],["dc.bibliographiccitation.journal","Circulation"],["dc.bibliographiccitation.lastpage","1696"],["dc.bibliographiccitation.volume","142"],["dc.contributor.author","Levent, Elif"],["dc.contributor.author","Noack, Claudia"],["dc.contributor.author","Zelarayán, Laura C."],["dc.contributor.author","Katschinski, Dörthe M."],["dc.contributor.author","Zimmermann, Wolfram-Hubertus"],["dc.contributor.author","Tiburcy, Malte"],["dc.date.accessioned","2021-04-14T08:31:23Z"],["dc.date.available","2021-04-14T08:31:23Z"],["dc.date.issued","2020"],["dc.identifier.doi","10.1161/CIRCULATIONAHA.119.044471"],["dc.identifier.pmid","33104400"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/83576"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/371"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation","SFB 1002 | C04: Fibroblasten-Kardiomyozyten Interaktion im gesunden und erkrankten Herzen: Mechanismen und therapeutische Interventionen bei Kardiofibroblastopathien"],["dc.relation","SFB 1002 | C07: Kardiomyozyten Wnt/β-catenin Komplex Aktivität im pathologischen Herz-Remodeling - als gewebespezifischer therapeutischer Ansatz"],["dc.relation","SFB 1002 | S01: In vivo und in vitro Krankheitsmodelle"],["dc.relation.eissn","1524-4539"],["dc.relation.issn","0009-7322"],["dc.relation.workinggroup","RG Tiburcy (Stem Cell Disease Modeling)"],["dc.relation.workinggroup","RG Zelarayán-Behrend (Developmental Pharmacology)"],["dc.relation.workinggroup","RG Zimmermann (Engineered Human Myocardium)"],["dc.title","Inhibition of Prolyl-Hydroxylase Domain Enzymes Protects From Reoxygenation Injury in Engineered Human Myocardium"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","455"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Cellular Physiology and Biochemistry"],["dc.bibliographiccitation.lastpage","462"],["dc.bibliographiccitation.volume","34"],["dc.contributor.author","Hesse, Amke R."],["dc.contributor.author","Levent, Elif"],["dc.contributor.author","Zieseniss, Anke"],["dc.contributor.author","Tiburcy, Malte"],["dc.contributor.author","Zimmermann, Wolfram-Hubertus"],["dc.contributor.author","Katschinski, Dörthe M."],["dc.date.accessioned","2017-09-07T11:46:54Z"],["dc.date.available","2017-09-07T11:46:54Z"],["dc.date.issued","2014"],["dc.description.abstract","Background/Aims: The hypoxia inducible factor-1 (HIF-1) is a suitable marker for tissue oxygenation. We intended to develop cardiomyocytes (CMs) expressing the oxygen-dependent degradation domain of HIE-la fused to the firefly luciferase (ODD-Luc) followed by proof-of-concept for its applicability in the assessment of heart muscle oxygenation. Methods and Results: We first generated embryonic stem cell (ESC) lines (ODD-Luc ESCs) from a Tg ROSA26 ODD-Luc/+ mouse. Subsequent CMs selection was facilitated by stable integration of an antibiotic resistance expressed under the control of the alpha MHC promoter. ODD-Luc ESCs showed a strong Luc-signal within 1 h of hypoxia (1% oxygen), which coincided with endogenous HIF-1 alpha. Engineered heart muscle (EHM) constructed with ODD-Luc CMs confirmed the utility of the model to sense hypoxia, and monitor reoxygenation also in a multicellular heart muscle model. Pharmacologically induced inotropy/chronotropy under isoprenaline resulted in enhanced Luc-signal suggesting enhanced oxygen consumption, leading to notable myocardial hypoxia. Conclusions: ODD-Luc-CMs can be used to monitor dynamic changes of cardiomyocyte oxygenation in living heart muscle samples. We provide proof-of-concept for pharmacologically induced myocardial interventions and envision applications of the developed model in drug screens and fundamental studies of ischemia/reperfusion injury. Copyright (C) 2014 S. Karger AG, Basel"],["dc.identifier.doi","10.1159/000363014"],["dc.identifier.gro","3142204"],["dc.identifier.isi","000343764600021"],["dc.identifier.pmid","25095893"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/11143"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/5688"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/123"],["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.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation","SFB 1002 | C04: Fibroblasten-Kardiomyozyten Interaktion im gesunden und erkrankten Herzen: Mechanismen und therapeutische Interventionen bei Kardiofibroblastopathien"],["dc.relation","SFB 1002 | S01: In vivo und in vitro Krankheitsmodelle"],["dc.relation.eissn","1421-9778"],["dc.relation.issn","1015-8987"],["dc.relation.workinggroup","RG Tiburcy (Stem Cell Disease Modeling)"],["dc.relation.workinggroup","RG Zimmermann (Engineered Human Myocardium)"],["dc.rights","CC BY-NC 3.0"],["dc.rights.uri","https://creativecommons.org/licenses/by-nc/3.0"],["dc.title","Lights on for HIF-1 alpha: Genetically Enhanced Mouse Cardiomyocytes for Heart Tissue Imaging"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]