Research Topics
Genomes and GenesSpecies | Eric MetzenSummaryCountry: Germany Publications
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Publications
Nitric oxide impairs normoxic degradation of HIF-1alpha by inhibition of prolyl hydroxylasesEric Metzen
Institute of Physiology, University of Luebeck, Germany
Mol Biol Cell 14:3470-81. 2003..We conclude that GSNO-attenuated prolyl hydroxylase activity accounts for HIF-1alpha accumulation under conditions of NO formation during normoxia and that PHD activity is subject to regulation by NO...
Inhibition of mitochondrial respiration elevates oxygen concentration but leaves regulation of hypoxia-inducible factor (HIF) intactKathrin Doege
Institute of Physiology, University of Lubeck, Lubeck, Germany
Blood 106:2311-7. 2005..Our data demonstrate that reduction of oxygen consumption reduces the O2 gradient in conventional cell cultures, causing elevation of the cellular O2 concentration, which leads to degradation of HIF-alpha...
Intracellular localisation of human HIF-1 alpha hydroxylases: implications for oxygen sensingEric Metzen
Institute of Physiology, University of Lubeck, Ratzeburger Allee 160, D 23538 Lubeck, Germany
J Cell Sci 116:1319-26. 2003..Endogenous PHD2mRNA and PHD3mRNA were hypoxia-inducible, whereas expression of PHD1mRNA and FIH-1mRNA was oxygen independent. We propose that PHDs and FIH-1 form an oxygen sensor cascade of distinct subcellular localisation...
HIF hydroxylation and cellular oxygen sensingEric Metzen
Institute of Physiology, University of Lubeck, Ratzeburger Allee 160, D 23538 Lubeck, Germany
Biol Chem 385:223-30. 2004..Regulation of the amount of hydroxylase protein, and the supply of other co-substrates and co-factors, particularly the cellular availability of iron, also contribute to tuning the physiological response to hypoxia...
Regulation of the prolyl hydroxylase domain protein 2 (phd2/egln-1) gene: identification of a functional hypoxia-responsive elementEric Metzen
Institute of Physiology, University of Luebeck, Ratzeburger Allee 160, D23538 Luebeck, Germany
Biochem J 387:711-7. 2005..We conclude that the phd2 gene is transcribed exclusively from the downstream promoter that contains a functional hypoxia-responsive, cis-regulatory element. Our results establish that PHD2 is a direct HIF target gene...
Hypoxia-inducible factor-1 (HIF-1) promotes its degradation by induction of HIF-alpha-prolyl-4-hydroxylasesJan H Marxsen
Department of Internal Medicine I, University of Luebeck, Ratzeburger Allee 160, D-23538 Luebeck, Germany
Biochem J 381:761-7. 2004..We propose a direct, negative regulatory mechanism, which limits accumulation of HIF-1alpha in hypoxia and leads to accelerated degradation on reoxygenation after long-term hypoxia...
The function of hypoxia-inducible factor (HIF) is independent of the endoplasmic reticulum protein OS-9Ulf Brockmeier
Institute of Physiology, University of Duisburg Essen, Essen, Germany
PLoS ONE 6:e19151. 2011..We conclude that OS-9 plays no direct functional role in HIF degradation since physical interaction of OS-9 with oxygen sensing HIF prolyl hydroxylases cannot occur in vivo due to their different subcellular localization...
Review: hypoxia-inducible factor-1 (HIF-1): a novel transcription factor in immune reactionsThomas Hellwig-Burgel
Institute of Physiology, University of Luebeck, D 23538 Luebeck, Germany
J Interferon Cytokine Res 25:297-310. 2005..The pharmacologic activation of the HIF-1 complex can be desirable in ischemic and inflammatory disorders. In contrast, HIF-1 blockade may be beneficial to prevent tumor angiogenesis and tumor growth...
Nuclear translocation of hypoxia-inducible factors (HIFs): involvement of the classical importin alpha/beta pathwayReinhard Depping
Department of Physiology, University of Lubeck, Ratzeburger Allee 160, D 23538 Lubeck, Germany
Biochim Biophys Acta 1783:394-404. 2008..In contrast, the supposed N-terminal NLS is not effective. Our findings provide new insight into the mechanism of the regulation of nuclear transport of hypoxia-inducible factors...
Stabilisation and knockdown of HIF--two distinct ways comparably important in radiotherapyMareike Ströfer
Department of Physiology, Center for Structural and Cell Biology in Medicine, University of Lubeck, Lubeck, Germany
Cell Physiol Biochem 28:805-12. 2011..The aim of the study was to examine cell type-specific effects of HIF-1α and -2α knockdown or oxygen-independent HIF-stabilisation on radiosensitivity...
Lack of functional erythropoietin receptors of cancer cell linesMagdalena Laugsch
Institute of Physiology, University of Luebeck, D 23538 Luebeck, Germany
Int J Cancer 122:1005-11. 2008..Apart from UT7/Epo, none of the tumor cell lines responded to Epo treatment with phosphorylation of signaling molecules or with cell proliferation...
Enzyme substrate recognition in oxygen sensing: how the HIF trap snapsEric Metzen
Institute of Physiology, University of Lubeck, Ratzeburger Allee 160, D23538 Lübeck, Federal Republic of Germany
Biochem J 408:e5-6. 2007..This elegant study improves our understanding of the interaction of the oxygen-sensing PHDs/EGLNs with their substrates, which include, but are not limited to, the HIFalpha proteins...
New insight into the SDF-1/CXCR4 axis in a breast carcinoma model: hypoxia-induced endothelial SDF-1 and tumor cell CXCR4 are required for tumor cell intravasationFengyan Jin
The First Hospital of Jilin University, Changchun, China
Mol Cancer Res 10:1021-31. 2012..Because both proteins were readily identifiable in a significant fraction of human breast cancer samples by immunohistochemistry, CXCR4 may constitute a molecular target for therapy when both, SDF-1, and CXCR4 are expressed...
Prolyl hydroxylase PHD3 activates oxygen-dependent protein aggregationKrista Rantanen
Turku Centre for Biotechnology, Turku University and Abo Akademi University, FIN 29521 Turku, Finland
Mol Biol Cell 19:2231-40. 2008..The data demonstrates the cellular oxygen sensor PHD3 as a regulator of protein aggregation in response to varying oxygen availability...
Chelation of cellular calcium modulates hypoxia-inducible gene expression through activation of hypoxia-inducible factor-1alphaUtta Berchner-Pfannschmidt
Institut fur Physiologie, Universitat Duisburg Essen, Hufelandstrasse 55, D 45122 Essen, Germany
J Biol Chem 279:44976-86. 2004..Instead, effective chelation of cellular calcium caused the accumulation of HIF-1alpha protein through inhibition of HIF-prolyl hydroxylases and activated HIF-1-dependent gene expression under normoxic conditions...
Nitric oxide reverses desferrioxamine- and hypoxia-evoked HIF-1alpha accumulation--implications for prolyl hydroxylase activity and ironMelvin Callapina
Faculty of Medicine, Institute of Biochemistry I, Johann Wolfgang Goethe-University, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany
Exp Cell Res 306:274-84. 2005..Variables that allow efficient PHD activation such as oxygen availability, iron content, or cofactor accessibility at that end allow NO to modulate HIF-1alpha accumulation...
Optical analysis of the HIF-1 complex in living cells by FRET and FRAPChristoph Wotzlaw
Institut fur Physiologie, Universitat Duisburg Essen, Hufelandstrasse 55, D 45122 Essen, Germany
FASEB J 21:700-7. 2007..2 nm, but even the N and C terminus of the HIF-1 complex were not further apart than 7.4 nm. Our data suggest a more compact 3-dimensional organization of the HIF complex than described so far by 2-dimensional models...
