Levent, Elif

[["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","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"]]