Krätzner, Ralph

[["dc.bibliographiccitation.firstpage","2100"],["dc.bibliographiccitation.issue","12"],["dc.bibliographiccitation.journal","European Journal of Organic Chemistry"],["dc.bibliographiccitation.lastpage","2106"],["dc.contributor.author","Pitulescu, Marian"],["dc.contributor.author","Grapp, Marcel"],["dc.contributor.author","Kraetzner, Ralph"],["dc.contributor.author","Knepel, Willhart"],["dc.contributor.author","Diederichsen, Ulf"],["dc.date.accessioned","2018-11-07T11:16:29Z"],["dc.date.available","2018-11-07T11:16:29Z"],["dc.date.issued","2008"],["dc.description.abstract","Two formacetal-linked dinucleotides TT and TT were synthesized as phosphoramidite building blocks for solid-phase synthesis. Incorporated in a 29-mer DNA, the oligomers P3(TT) and P3(TA) were studied with respect to the binding activity towards the Pax6 homeodomain. Substitution of the negatively charged phosphodiester by a neutral formacetal linker facilitates the bent conformation of double-stranded DNA. The duplex stability was affected more significantly by the TT formacetal modification, whereas destabilization induced by TA was less pronounced. Based on CD spectroscopy, the TA formacetal-modified oligomer P3(TA) A has mainly B-DNA topology, whereas the P3(TT) modified oligomet significantly deviated from B-form DNA. The binding affinity of the P3 oligomer towards Pax6 HD was investigated by in vitro EMSA experiments providing even a small increase in binding affinity for the P3(TA) T oligomer. ((C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)."],["dc.identifier.doi","10.1002/ejoc.200701178"],["dc.identifier.isi","000255508600010"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/54599"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-blackwell"],["dc.relation.issn","1434-193X"],["dc.title","Synthesis of formacetal-linked dinucleotides to facilitate dsDNA bending and binding to the homeodomain of Pax6"],["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","375"],["dc.contributor.author","Oetjen, Elke"],["dc.contributor.author","Blume, Roland"],["dc.contributor.author","Cierny, I."],["dc.contributor.author","Kutschenko, Anna"],["dc.contributor.author","Kraetzner, Ralph"],["dc.contributor.author","Stein, R."],["dc.contributor.author","Knepel, Willhart"],["dc.date.accessioned","2018-11-07T11:04:44Z"],["dc.date.available","2018-11-07T11:04:44Z"],["dc.date.issued","2007"],["dc.format.extent","49"],["dc.identifier.isi","000245997000216"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/51901"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Springer"],["dc.publisher.place","New york"],["dc.relation.conference","48th Spring Meeting of the Deutsche-Gesellschaft-fur Experimentelle-ung-Klinische-Pharmakologie-und-Toxikologie"],["dc.relation.eventlocation","Mainz, GERMANY"],["dc.relation.issn","0028-1298"],["dc.title","Inhibition of MafA transcriptional activity contributes to the inhibition of human insulin gene transcription by MEKK1 and interleukin-1beta"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1678"],["dc.bibliographiccitation.issue","8"],["dc.bibliographiccitation.journal","Diabetologia"],["dc.bibliographiccitation.lastpage","1687"],["dc.bibliographiccitation.volume","50"],["dc.contributor.author","Oetjen, Elke"],["dc.contributor.author","Blume, Roland"],["dc.contributor.author","Cierny, I."],["dc.contributor.author","Schlag, C."],["dc.contributor.author","Kutschenko, Anna"],["dc.contributor.author","Kraetzner, Ralph"],["dc.contributor.author","Stein, R."],["dc.contributor.author","Knepel, Willhart"],["dc.date.accessioned","2018-11-07T10:59:51Z"],["dc.date.available","2018-11-07T10:59:51Z"],["dc.date.issued","2007"],["dc.description.abstract","Aims/hypothesis Inappropriate insulin secretion and biosynthesis are hallmarks of beta cell dysfunction and contribute to the progression from a prediabetic state to overt diabetes mellitus. During the prediabetic state, beta cells are exposed to elevated levels of proinflammatory cytokines. In the present study the effect of these cytokines and mitogen-activated protein kinase kinase kinase 1 (MEKK1), which is known to be activated by these cytokines, on human insulin gene (INS) transcription was investigated. Methods Biochemical methods and reporter gene assays were used in a beta cell line and in primary pancreatic islets from transgenic mice. Results IL-1 beta and MEKK1 specifically inhibited basal and membrane depolarisation and cAMP-induced INS transcription in the beta cell line. Also, in primary islets of reporter gene mice, IL-1 beta reduced glucose-stimulated INS transcription. A 5'- and 3'-deletion and internal mutation analysis revealed the rat insulin promoter element 3b (RIPE3b) to be a decisive MEKK1-responsive element of the INS. RIPE3b conferred strong transcriptional activity to a heterologous promoter, and this activity was markedly inhibited by MEKK1 and IL-1 beta. RIPE3b is also known to recruit the transcription factor MafA. We found here that MafA transcription activity is markedly inhibited by MEKK1 and IL-1 beta. Conclusions/interpretation These data suggest that IL-1 beta through MEKK1 inhibits INS transcription and does so, at least in part, by decreasing MafA transcriptional activity at the RIPE3b control element. Since inappropriate insulin biosynthesis contributes to beta cell dysfunction, inhibition of MEKK1 might decelerate or prevent progression from a prediabetic state to diabetes mellitus."],["dc.description.sponsorship","PHS HHS [NIH 42502]"],["dc.identifier.doi","10.1007/s00125-007-0712-2"],["dc.identifier.isi","000248225100014"],["dc.identifier.pmid","17583797"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/50792"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Springer"],["dc.relation.issn","0012-186X"],["dc.title","Inhibition of MafA transcriptional activity and human insulin gene transcription by interleukin-1 beta and mitogen-activated protein kinase kinase kinase in pancreatic islet beta cells"],["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","371"],["dc.contributor.author","Kratzner, R."],["dc.contributor.author","Schinner, S."],["dc.contributor.author","Schlenczek, S."],["dc.contributor.author","Dickel, Corinna"],["dc.contributor.author","Knepel, Willhart"],["dc.date.accessioned","2018-11-07T08:29:30Z"],["dc.date.available","2018-11-07T08:29:30Z"],["dc.date.issued","2005"],["dc.format.extent","R66"],["dc.identifier.isi","000229046800280"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/16669"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Springer"],["dc.publisher.place","New york"],["dc.relation.eventlocation","Mainz, GERMANY"],["dc.relation.issn","0028-1298"],["dc.title","Effect of rosiglitazone and ppar gamma on human insulin gene transcription"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","403"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms"],["dc.bibliographiccitation.lastpage","412"],["dc.bibliographiccitation.volume","1789"],["dc.contributor.author","Grapp, Marcel"],["dc.contributor.author","Teichler, Sabine"],["dc.contributor.author","Kitz, Julia"],["dc.contributor.author","Dibaj, Payam"],["dc.contributor.author","Dickel, Corinna"],["dc.contributor.author","Knepel, Willhart"],["dc.contributor.author","Kraetzner, Ralph"],["dc.date.accessioned","2018-11-07T08:30:08Z"],["dc.date.available","2018-11-07T08:30:08Z"],["dc.date.issued","2009"],["dc.description.abstract","The transcription factor PAX6 plays an important role in transcriptional regulation of the peptide hormone glucagon from pancreatic alpha-cells. PAX6 contains two DNA binding domains, the paired domain (PD) and the homeodomain (HD). While the interaction of the PD with the PAX6 responsive elements G1 and G3 in the rat glucagon gene promoter is well understood, the role of the PAX6 HD for PAX6 binding and function on G1 and G3 remains unclear. In EMSA studies the PAX6 HD was found to be mandatory for PAX6 binding to G1 but not to G3. Transient transfections with luciferase reporter gene constructs revealed the HD to be critical for proper function of PAX6 on both, G1 and G3. Transfection data with variant promoter constructs and limited proteolysis assays demonstrated that the DNA sequence located 5' to the PD binding site plays an important role for PAX6 function and its conformation on the elements G1 and G3. Taken together, our data indicate a PH0-like binding of PAX6 to the glucagon promoter elements G1 and G3 where the HD binding site is abutted directly to the PD binding motif The data suggest that the PH0-like binding induces a transcriptionally active conformation of PAX6. (C) 2009 Elsevier B.V. All rights reserved."],["dc.description.sponsorship","Deutsche Forschungsgemeinschaft [SFB402/A3]"],["dc.identifier.doi","10.1016/j.bbagrm.2009.02.001"],["dc.identifier.isi","000267466400004"],["dc.identifier.pmid","19217949"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/16821"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Elsevier Science Bv"],["dc.relation.issn","1874-9399"],["dc.title","The homeodomain of PAX6 is essential for PAX6-dependent activation of the rat glucagon gene promoter: Evidence for a PH0-like binding that induces an active conformation"],["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","372"],["dc.contributor.author","Grapp, Marcel"],["dc.contributor.author","Kratzner, R."],["dc.contributor.author","Teichler, S."],["dc.contributor.author","Knepel, Willhart"],["dc.date.accessioned","2018-11-07T10:14:51Z"],["dc.date.available","2018-11-07T10:14:51Z"],["dc.date.issued","2006"],["dc.format.extent","71"],["dc.identifier.isi","000237126800258"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/40702"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Springer"],["dc.publisher.place","New york"],["dc.relation.conference","47th Spring Meeting of the Deutsche-Gesellschaft-fur-Experimentelle-und-Klinische-Pharmakologie-und Toxikologie"],["dc.relation.eventlocation","Mainz, GERMANY"],["dc.relation.issn","0028-1298"],["dc.title","Role of the PAX6 homeodomain in regulation of glucagon gene transcrition"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","509"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Molecular Pharmacology"],["dc.bibliographiccitation.lastpage","517"],["dc.bibliographiccitation.volume","73"],["dc.contributor.author","Kraetzner, Ralph"],["dc.contributor.author","Froehlich, Florian"],["dc.contributor.author","Lepler, Katrin"],["dc.contributor.author","Schroeder, Michaela"],["dc.contributor.author","Roeher, Katharina"],["dc.contributor.author","Dickel, Corinna"],["dc.contributor.author","Tzvetkov, Mladen Vassilev"],["dc.contributor.author","Quentin, Thomas"],["dc.contributor.author","Oetjen, Elke"],["dc.contributor.author","Knepel, Willhart"],["dc.date.accessioned","2018-11-07T11:18:50Z"],["dc.date.available","2018-11-07T11:18:50Z"],["dc.date.issued","2008"],["dc.description.abstract","The peptide hormone glucagon stimulates hepatic glucose output, and its levels in the blood are elevated in type 2 diabetes mellitus. The nuclear receptor peroxisome proliferator-activated receptor-gamma (PPAR gamma) has essential roles in glucose homeostasis, and thiazolidinedione PPAR gamma agonists are clinically important antidiabetic drugs. As part of their antidiabetic effect, thiazolidinediones such as rosiglitazone have been shown to inhibit glucagon gene transcription through binding to PPAR gamma and inhibition of the transcriptional activity of PAX6 that is required for cell-specific activation of the glucagon gene. However, how thiazolidinediones and PPAR gamma inhibit PAX6 activity at the glucagon promoter remained unknown. After transient transfection of a glucagon promoter-reporter fusion gene into a glucagon-producing pancreatic islet alpha-cell line, ligand-bound PPAR gamma was found in the present study to inhibit glucagon gene transcription also after deletion of its DNA-binding domain. Like PPAR gamma ligands, also retinoid X receptor (RXR) agonists inhibited glucagon gene transcription in a PPAR gamma-dependent manner. In glutathione transferase pull-down assays, the ligand-bound PPAR gamma-RXR heterodimer bound to the transactivation domain of PAX6. This interaction depended on the presence of the ligand and RXR, but it was independent of the PPAR gamma DNA-binding domain. Chromatin immunoprecipitation experiments showed that PPAR gamma is recruited to the PAX6-binding proximal glucagon promoter. Taken together, the results of the present study support a model in which a ligand-bound PPAR gamma-RXR heterodimer physically interacts with promoter-bound PAX6 to inhibit glucagon gene transcription. These data define PAX6 as a novel physical target of PPAR gamma-RXR."],["dc.identifier.doi","10.1124/mol.107.035568"],["dc.identifier.isi","000252597300025"],["dc.identifier.pmid","17962386"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/55129"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Soc Pharmacology Experimental Therapeutics"],["dc.relation.issn","0026-895X"],["dc.title","A peroxisome proliferator-activated receptor gamma-retinoid X receptor heterodimer physically interacts with the transcriptional activator PAX6 to inhibit glucagon gene transcription"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]