Farhat, Katja

[["dc.bibliographiccitation.firstpage","33756"],["dc.bibliographiccitation.issue","44"],["dc.bibliographiccitation.journal","Journal of Biological Chemistry"],["dc.bibliographiccitation.lastpage","33763"],["dc.bibliographiccitation.volume","285"],["dc.contributor.author","Vogel, Sabine"],["dc.contributor.author","Wottawa, Marieke"],["dc.contributor.author","Farhat, Katja"],["dc.contributor.author","Zieseniss, Anke"],["dc.contributor.author","Schnelle, Moritz"],["dc.contributor.author","Le-Huu, Sinja"],["dc.contributor.author","von Ahlen, Melanie"],["dc.contributor.author","Malz, Cordula R."],["dc.contributor.author","Camenisch, Gieri"],["dc.contributor.author","Katschinski, Doerthe Magdalena"],["dc.date.accessioned","2018-11-07T08:37:53Z"],["dc.date.available","2018-11-07T08:37:53Z"],["dc.date.issued","2010"],["dc.description.abstract","Cells are responding to hypoxia via prolyl-4-hydroxylase domain (PHD) enzymes, which are responsible for oxygen-dependent hydroxylation of the hypoxia-inducible factor (HIF)-1 alpha subunit. To gain further insight into PHD function, we generated knockdown cell models for the PHD2 isoform, which is the main isoform regulating HIF-1 alpha hydroxylation and thus stability in normoxia. Induction of a PHD2 knockdown in tetracycline-inducible HeLa PHD2 knockdown cells resulted in increased F-actin formation as detected by phalloidin staining. A similar effect could be observed in the stably transfected PHD2 knockdown cell clones 1B6 and 3B7. F-actin is at least in part responsible for shaping cell morphology as well as regulating cell migration. Cell migration was impaired significantly as a consequence of PHD2 knockdown in a scratch assay. Mechanistically, PHD2 knockdown resulted in activation of the RhoA (Ras homolog gene family member A)/Rho-associated kinase pathway with subsequent phosphorylation of cofilin. Because cofilin phosphorylation impairs its actin-severing function, this may explain the F-actin phenotype, thereby providing a functional link between PHD2-dependent signaling and cell motility."],["dc.identifier.doi","10.1074/jbc.M110.132985"],["dc.identifier.isi","000283354000021"],["dc.identifier.pmid","20801873"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/6193"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/18648"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Soc Biochemistry Molecular Biology Inc"],["dc.relation.issn","0021-9258"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Prolyl Hydroxylase Domain (PHD) 2 Affects Cell Migration and F-actin Formation via RhoA/Rho-associated Kinase-dependent Cofilin Phosphorylation"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","365"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Journal of Leukocyte Biology"],["dc.bibliographiccitation.lastpage","375"],["dc.bibliographiccitation.volume","96"],["dc.contributor.author","Swain, Lija"],["dc.contributor.author","Wottawa, Marieke"],["dc.contributor.author","Hillemann, Annette"],["dc.contributor.author","Beneke, Angelika"],["dc.contributor.author","Odagiri, Haruki"],["dc.contributor.author","Terada, Kazutoyo"],["dc.contributor.author","Endo, Motoyoshi"],["dc.contributor.author","Oike, Yuichi"],["dc.contributor.author","Farhat, Katja"],["dc.contributor.author","Katschinski, Doerthe Magdalena"],["dc.date.accessioned","2018-11-07T09:36:09Z"],["dc.date.available","2018-11-07T09:36:09Z"],["dc.date.issued","2014"],["dc.description.abstract","On a molecular level, cells sense changes in oxygen availability through the PHDs, which regulate the protein stability of the alpha-subunit of the transcription factor HIF. Especially, PHD3 has been additionally associated with apoptotic cell death. We hypothesized that PHD3 plays a role in cell-fate decisions in macrophages. Therefore, myeloid-specific PHD3(-/-) mice were created and analyzed. PHD3(-/-) BMDM showed no altered HIF-1 alpha or HIF-2 alpha stabilization or increased HIF target gene expression in normoxia or hypoxia. Macrophage M1 and M2 polarization was unchanged likewise. Compared with macrophages from WT littermates, PHD3(-/-) BMDM exhibited a significant reduction in TUNEL-positive cells after serum withdrawal or treatment with stauro and SNAP. Under the same conditions, PHD3(-/-) BMDM also showed less Annexin V staining, which is representative for membrane disruption, and indicated a reduced early apoptosis. In an unbiased transcriptome screen, we found that Angptl2 expression was reduced in PHD3(-/-) BMDM under stress conditions. Addition of rAngptl2 rescued the antiapoptotic phenotype, demonstrating that it is involved in the PHD3-mediated response toward apoptotic stimuli in macrophages."],["dc.identifier.doi","10.1189/jlb.2HI1013-533R"],["dc.identifier.isi","000340829400003"],["dc.identifier.pmid","24626957"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/32548"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Federation Amer Soc Exp Biol"],["dc.relation.issn","1938-3673"],["dc.relation.issn","0741-5400"],["dc.title","Prolyl-4-hydroxylase domain 3 (PHD3) is a critical terminator for cell survival of macrophages under stress conditions"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["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 prüfen"],["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"]]

[["dc.bibliographiccitation.artnumber","e69128"],["dc.bibliographiccitation.issue","7"],["dc.bibliographiccitation.journal","PLoS ONE"],["dc.bibliographiccitation.volume","8"],["dc.contributor.author","Vogler, Melanie"],["dc.contributor.author","Vogel, Sabine"],["dc.contributor.author","Krull, Sabine"],["dc.contributor.author","Farhat, Katja"],["dc.contributor.author","Leisering, Pia"],["dc.contributor.author","Lutz, Susanne"],["dc.contributor.author","Wuertz, Christina M."],["dc.contributor.author","Katschinski, Doerthe Magdalena"],["dc.contributor.author","Zieseniss, Anke"],["dc.date.accessioned","2018-11-07T09:22:20Z"],["dc.date.available","2018-11-07T09:22:20Z"],["dc.date.issued","2013"],["dc.description.abstract","Cells can adapt to hypoxia by various mechanisms. Yet, hypoxia-induced effects on the cytoskeleton-based cell architecture and functions are largely unknown. Here we present a comprehensive analysis of the architecture and function of L929 fibroblasts under hypoxic conditions (1% O-2). Cells cultivated in hypoxia showed striking morphological differences as compared to cells cultivated under normoxic conditions (20% O-2). These changes include an enlargement of cell area and volume, increased numbers of focal contacts and loss of cell polarization. Furthermore the beta- and gamma-actin distribution is greatly altered. These hypoxic adjustments are associated with enhanced cell spreading and a decline of cell motility in wound closure and single cell motility assays. As the hypoxia-inducible factor-1 alpha (HIF-1 alpha) is stabilised in hypoxia and plays a pivotal role in the transcriptional response to changes in oxygen availability we used an shRNA-approach to examine the role of HIF-1 alpha in cytoskeleton-related architecture and functions. We show that the observed increase in cell area, actin filament rearrangement, decrease of single cell migration in hypoxia and the maintenance of p-cofilin levels is dependent on HIF-1 alpha stabilisation."],["dc.identifier.doi","10.1371/journal.pone.0069128"],["dc.identifier.isi","000324146200061"],["dc.identifier.pmid","23874890"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/9965"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/29319"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Public Library Science"],["dc.relation.issn","1932-6203"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Hypoxia Modulates Fibroblastic Architecture, Adhesion and Migration: A Role for HIF-1 alpha in Cofilin Regulation and Cytoplasmic Actin Distribution"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","77"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Cardiovascular Research"],["dc.bibliographiccitation.lastpage","86"],["dc.bibliographiccitation.volume","94"],["dc.contributor.author","Hoelscher, Marion"],["dc.contributor.author","Schaefer, Katrin"],["dc.contributor.author","Krull, Sabine"],["dc.contributor.author","Farhat, Katja"],["dc.contributor.author","Hesse, Amke"],["dc.contributor.author","Silter, Monique"],["dc.contributor.author","Lin, Yun"],["dc.contributor.author","Pichler, Bernd J."],["dc.contributor.author","Thistlethwaite, Patricia"],["dc.contributor.author","El-Armouche, Ali"],["dc.contributor.author","Maier, Lars. S."],["dc.contributor.author","Katschinski, Doerthe Magdalena"],["dc.contributor.author","Zieseniss, Anke"],["dc.date.accessioned","2018-11-07T09:11:48Z"],["dc.date.available","2018-11-07T09:11:48Z"],["dc.date.issued","2012"],["dc.description.abstract","The hypoxia-inducible factor-1 (HIF-1) is the master modulator of hypoxic gene expression. The effects of chronically stabilized cardiac HIF-1 and its role in the diseased heart are not precisely known. The aims of this study were as follows: (i)to elucidate consequences of HIF-1 stabilization in the heart; (ii)to analyse long-term effects of HIF-1 stabilization with ageing and the ability of the HIF-1 overexpressing hearts to respond to increased mechanical load; and (iii)to analyse HIF-1 protein levels in failing heart samples. In a cardiac-specific HIF-1 transgenic mouse model, constitutive expression of HIF-1 leads to changes in capillary area and shifts the cardiac metabolism towards glycolysis with a net increase in glucose uptake. Furthermore, Ca-2 handling is altered, with increased Ca-2 transients and faster intracellular [Ca-2] decline. These changes are associated with decreased expression of sarcoplasmic/endoplasmic reticulum calcium ATPase 2a but elevated phosphorylation of phospholamban. HIF-1 transgenic mice subjected to transverse aortic constriction exhibited profound cardiac decompensation. Moreover, cardiomyopathy was also seen in ageing transgenic mice. In parallel, we found an increased stabilization of HIF-1 in heart samples of patients with end-stage heart failure. Changes induced with transgenic cardiac HIF-1 possibly mediate beneficial effects in the short term; however, with increased mechanical load and ageing they become detrimental for cardiac function. Together with the finding of increased HIF-1 protein levels in samples from human patients with cardiomyopathy, these data indicate that chronic HIF-1 stabilization drives autonomous pathways that add to disease progression."],["dc.identifier.doi","10.1093/cvr/cvs014"],["dc.identifier.isi","000301983100012"],["dc.identifier.pmid","22258630"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/26804"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Oxford Univ Press"],["dc.relation.issn","0008-6363"],["dc.title","Unfavourable consequences of chronic cardiac HIF-1 stabilization"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","3426"],["dc.bibliographiccitation.issue","17"],["dc.bibliographiccitation.journal","Molecular and Cellular Biology"],["dc.bibliographiccitation.lastpage","3438"],["dc.bibliographiccitation.volume","33"],["dc.contributor.author","Kalucka, Joanna"],["dc.contributor.author","Ettinger, Andreas"],["dc.contributor.author","Franke, Kristin"],["dc.contributor.author","Mamlouk, Soulafa"],["dc.contributor.author","Singh, Rashim Pal"],["dc.contributor.author","Farhat, Katja"],["dc.contributor.author","Muschter, Antje"],["dc.contributor.author","Olbrich, Susanne"],["dc.contributor.author","Breier, Georg"],["dc.contributor.author","Katschinski, Doerthe Magdalena"],["dc.contributor.author","Huttner, Wieland"],["dc.contributor.author","Weidemann, Alexander"],["dc.contributor.author","Wielockx, Ben"],["dc.date.accessioned","2018-11-07T09:20:59Z"],["dc.date.available","2018-11-07T09:20:59Z"],["dc.date.issued","2013"],["dc.description.abstract","Skin wound healing in mammals is a complex, multicellular process that depends on the precise supply of oxygen. Hypoxia-inducible factor (HIF) prolyl hydroxylase 2 (PHD2) serves as a crucial oxygen sensor and may therefore play an important role during reepithelialization. Hence, this study was aimed at understanding the role of PHD2 in cutaneous wound healing using different lines of conditionally deficient mice specifically lacking PHD2 in inflammatory, vascular, or epidermal cells. Interestingly, PHD2 deficiency only in keratinocytes and not in myeloid or endothelial cells was found to lead to faster wound closure, which involved enhanced migration of the hyperproliferating epithelium. We demonstrate that this effect relies on the unique expression of beta(3)-integrin in the keratinocytes around the tip of the migrating tongue in an HIF1 alpha-dependent manner. Furthermore, we show enhanced proliferation of these cells in the stratum basale, which is directly related to their attenuated transforming growth factor beta signaling. Thus, loss of the central oxygen sensor PHD2 in keratinocytes stimulates wound closure by prompting skin epithelial cells to migrate and proliferate. Inhibition of PHD2 could therefore offer novel therapeutic opportunities for the local treatment of cutaneous wounds."],["dc.identifier.doi","10.1128/MCB.00609-13"],["dc.identifier.isi","000322817600004"],["dc.identifier.pmid","23798557"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/29006"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Soc Microbiology"],["dc.relation.issn","0270-7306"],["dc.title","Loss of Epithelial Hypoxia-Inducible Factor Prolyl Hydroxylase 2 Accelerates Skin Wound Healing in Mice"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","e00236"],["dc.bibliographiccitation.firstpage","e00236"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Molecular and Cellular Biology"],["dc.bibliographiccitation.lastpage","16"],["dc.bibliographiccitation.volume","37"],["dc.contributor.author","Guentsch, Annemarie"],["dc.contributor.author","Beneke, Angelika"],["dc.contributor.author","Swain, Lija"],["dc.contributor.author","Farhat, Katja"],["dc.contributor.author","Nagarajan, Shunmugam"],["dc.contributor.author","Wielockx, Ben"],["dc.contributor.author","Raithatha, Kaamini"],["dc.contributor.author","Dudek, Jan"],["dc.contributor.author","Rehling, Peter"],["dc.contributor.author","Katschinski, Dörthe M."],["dc.date.accessioned","2021-06-01T10:47:35Z"],["dc.date.available","2021-06-01T10:47:35Z"],["dc.date.issued","2016"],["dc.description.abstract","ABSTRACT The prolyl-4-hydroxylase domain (PHD) enzymes are regarded as the molecular oxygen sensors. There is an interplay between oxygen availability and cellular metabolism, which in turn has significant effects on the functionality of innate immune cells, such as macrophages. However, if and how PHD enzymes affect macrophage metabolism are enigmatic. We hypothesized that macrophage metabolism and function can be controlled via manipulation of PHD2. We characterized the metabolic phenotypes of PHD2-deficient RAW cells and primary PHD2 knockout bone marrow-derived macrophages (BMDM). Both showed typical features of anaerobic glycolysis, which were paralleled by increased pyruvate dehydrogenase kinase 1 (PDK1) protein levels and a decreased pyruvate dehydrogenase enzyme activity. Metabolic alterations were associated with an impaired cellular functionality. Inhibition of PDK1 or knockout of hypoxia-inducible factor 1α (HIF-1α) reversed the metabolic phenotype and impaired the functionality of the PHD2-deficient RAW cells and BMDM. Taking these results together, we identified a critical role of PHD2 for a reversible glycolytic reprogramming in macrophages with a direct impact on their function. We suggest that PHD2 serves as an adjustable switch to control macrophage behavior."],["dc.identifier.doi","10.1128/MCB.00236-16"],["dc.identifier.gro","3145080"],["dc.identifier.pmid","27795296"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/85650"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-425"],["dc.notes.status","final"],["dc.relation.eissn","1098-5549"],["dc.relation.issn","0270-7306"],["dc.subject","PDK; dioxygenases; hypoxia; macrophages; prolyl-4-hydroxylase domain"],["dc.title","PHD2 Is a Regulator for Glycolytic Reprogramming in Macrophages"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","no"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Acta Physiologica"],["dc.bibliographiccitation.volume","216"],["dc.contributor.author","Guentsch, Annemarie"],["dc.contributor.author","Beneke, Angelika"],["dc.contributor.author","Farhat, Katja"],["dc.contributor.author","Swain, Lija"],["dc.contributor.author","Hillemann, Annette"],["dc.contributor.author","Nagarajan, S."],["dc.contributor.author","Dudek, Jan"],["dc.contributor.author","Shah, Ajay M."],["dc.contributor.author","Katschinski, Doerthe Magdalena"],["dc.date.accessioned","2018-11-07T10:17:27Z"],["dc.date.available","2018-11-07T10:17:27Z"],["dc.date.issued","2016"],["dc.identifier.isi","000372285400087"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/41228"],["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","The oxygen sensor PHD2 affects cell migration, energy metabolism and mitochondrial function in macrophages"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]