Farhat, Katja

[["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.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"]]