Now showing 1 - 2 of 2
  • 2011Journal Article
    [["dc.bibliographiccitation.firstpage","11185"],["dc.bibliographiccitation.issue","13"],["dc.bibliographiccitation.journal","Journal of Biological Chemistry"],["dc.bibliographiccitation.lastpage","11194"],["dc.bibliographiccitation.volume","286"],["dc.contributor.author","Hoelscher, Marion"],["dc.contributor.author","Silter, Monique"],["dc.contributor.author","Krull, Sabine"],["dc.contributor.author","von Ahlen, Melanie"],["dc.contributor.author","Hesse, Amke"],["dc.contributor.author","Schwartz, Peter J."],["dc.contributor.author","Wielockx, Ben"],["dc.contributor.author","Breier, Georg"],["dc.contributor.author","Katschinski, Doerthe Magdalena"],["dc.contributor.author","Zieseniss, Anke"],["dc.date.accessioned","2018-11-07T08:57:35Z"],["dc.date.available","2018-11-07T08:57:35Z"],["dc.date.issued","2011"],["dc.description.abstract","Prolylhydroxylase domain proteins (PHD) are cellular oxygen- sensing molecules that regulate the stability of the alpha-subunit of the transcription factor hypoxia inducible factor (HIF)-1. HIF-1 affects cardiac development as well as adaptation of the heart toward increased pressure overload or myocardial infarction. We have disrupted PHD2 in cardiomyocytes (cPhd(-/-)) using Phd2(flox/flox) mice in combination with MLCvCre mice, which resulted in HIF-1 alpha stabilization and activation of HIF target genes in the heart. Although cPhd2(-/-) mice showed no gross abnormalities in cardiac filament structure or function, we observed a significant increased cardiac capillary area in those mice. cPhd2(-/-) mice did not respond differently to increased mechanical load by transverse aortic constriction compared with their wild-type (wt) littermates. After ligation of the left anterior descending artery, however, the area at risk and area of necrosis were significantly smaller in the cPhd2(-/-) mice compared with Phd2 wt mice in line with the described pivotal role of HIF-1 alpha for tissue protection in case of myocardial infarction. This correlated with a decreased number of apoptotic cells in the infarcted myocardium in the cPhd2(-/-) mice and significantly improved cardiac function 3 weeks after myocardial infarction."],["dc.identifier.doi","10.1074/jbc.M110.186809"],["dc.identifier.isi","000288797100029"],["dc.identifier.pmid","21270129"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/23434"],["dc.notes.status","zu prĂĽfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Soc Biochemistry Molecular Biology Inc"],["dc.relation.issn","0021-9258"],["dc.title","Cardiomyocyte-specific Prolyl-4-hydroxylase Domain 2 Knock Out Protects from Acute Myocardial Ischemic Injury"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]
    Details DOI PMID PMC WOS
  • 2013Journal Article
    [["dc.bibliographiccitation.firstpage","2787"],["dc.bibliographiccitation.issue","12"],["dc.bibliographiccitation.journal","International Journal of Cancer"],["dc.bibliographiccitation.lastpage","2798"],["dc.bibliographiccitation.volume","132"],["dc.contributor.author","Wottawa, Marieke"],["dc.contributor.author","Leisering, Pia"],["dc.contributor.author","von Ahlen, Melanie"],["dc.contributor.author","Schnelle, Moritz"],["dc.contributor.author","Vogel, Sabine"],["dc.contributor.author","Malz, Cordula R."],["dc.contributor.author","Bordoli, Mattia Renato"],["dc.contributor.author","Camenisch, Gieri"],["dc.contributor.author","Hesse, Amke"],["dc.contributor.author","Napp, Joanna"],["dc.contributor.author","Alves, Frauke"],["dc.contributor.author","Kristiansen, Glen"],["dc.contributor.author","Farhat, Katja"],["dc.contributor.author","Katschinski, Doerthe Magdalena"],["dc.date.accessioned","2018-11-07T09:23:40Z"],["dc.date.available","2018-11-07T09:23:40Z"],["dc.date.issued","2013"],["dc.description.abstract","The prolyl-4-hydroxylase domain 13 (PHD13) enzymes are regulating the protein stability of the -subunit of the hypoxia-inducible factor-1 (HIF-1), which mediates oxygen-dependent gene expression. PHD2 is the main isoform regulating HIF-1 hydroxylation and thus stability in normoxia. In human cancers, HIF-1 is overexpressed as a result of intratumoral hypoxia which in turn promotes tumor progression. The role of PHD2 for tumor progression is in contrast far from being thoroughly understood. Therefore, we established PHD2 knockdown clones of MDA-MB-231 breast cancer cells and analyzed their tumor-forming potential in a SCID mouse model. Tumor progression was significantly impaired in the PHD2 knockdown MDA-MB-231 cells, which could be partially rescued by re-establishing PHD2 expression. In a RNA profile screen, we identified the secreted phosphoprotein 1 (SPP1) as one target, which is differentially regulated as a consequence of the PHD2 knockdown. Knockdown of PHD2 drastically reduced the SPP1 expression in MDA-MB-231 cells. A correlation of SPP1 and PHD2 expression was additionally verified in 294 invasive breast cancer biopsies. In subsequent analyses, we identified that PHD2 alters the processing of transforming growth factor (TGF)-1, which is highly involved in SPP1 expression. The altered processing capacity was associated with a dislocation of the pro-protein convertase furin. Thus, our data demonstrate that in MDA-MB-231 cells PHD2 might affect tumor-relevant TGF-1 target gene expression by altering the TGF-1 processing capacity."],["dc.description.sponsorship","Wilhelm Sander Stiftung [1348530]"],["dc.identifier.doi","10.1002/ijc.27982"],["dc.identifier.isi","000317593100008"],["dc.identifier.pmid","23225569"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/29634"],["dc.notes.status","zu prĂĽfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-blackwell"],["dc.relation.issn","0020-7136"],["dc.title","Knockdown of prolyl-4-hydroxylase domain 2 inhibits tumor growth of human breast cancer MDA-MB-231 cells by affecting TGF-1 processing"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]
    Details DOI PMID PMC WOS