ArticleCell metabolism2016
Deletion or Inhibition of the Oxygen Sensor PHD1 Protects against Ischemic Stroke via Reprogramming of Neuronal Metabolism.
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Article in Cell metabolism, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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53citing papers in PubMed
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53 citing papers in PubMed, 96 citations in OpenAlex.
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Authors and funding
31 authors at 6 institutions in 3 countries.
Annelies QuaegebeurLaboratory of Angiogenesis and Neurovascular link, Department of Oncology, University of Leuven, Leuven, Belgium; Laboratory of Angiogenesis and Neurovascular link, Vesalius Research Center, VIB, Leuven, Belgium.
Inmaculada SeguraLaboratory of Angiogenesis and Neurovascular link, Department of Oncology, University of Leuven, Leuven, Belgium; Laboratory of Angiogenesis and Neurovascular link, Vesalius Research Center, VIB, Leuven, Belgium.
Roberta SchmiederLaboratory of Cellular Metabolism and Metabolic Regulation, Department of Oncology, University of Leuven, Leuven, Belgium; Laboratory of Cellular Metabolism and Metabolic Regulation, Vesalius Research Center, VIB, Leuven, Belgium.
Dries VerdegemLaboratory of Angiogenesis and Neurovascular link, Department of Oncology, University of Leuven, Leuven, Belgium; Laboratory of Angiogenesis and Neurovascular link, Vesalius Research Center, VIB, Leuven, Belgium; Metabolomics Expertise Center, Vesalius Research Center, VIB, Leuven, Belgium.
Ilaria DecimoLaboratory of Angiogenesis and Neurovascular link, Department of Oncology, University of Leuven, Leuven, Belgium; Laboratory of Angiogenesis and Neurovascular link, Vesalius Research Center, VIB, Leuven, Belgium.
Francesco BifariLaboratory of Angiogenesis and Neurovascular link, Department of Oncology, University of Leuven, Leuven, Belgium; Laboratory of Angiogenesis and Neurovascular link, Vesalius Research Center, VIB, Leuven, Belgium.
Tom DresselaersBiomedical MRI/Mosaic, Department of Imaging and Pathology, University of Leuven, Leuven, Belgium.
Guy EelenLaboratory of Angiogenesis and Neurovascular link, Department of Oncology, University of Leuven, Leuven, Belgium; Laboratory of Angiogenesis and Neurovascular link, Vesalius Research Center, VIB, Leuven, Belgium.
Debapriva GhoshLaboratory of Ion Channel Research and TRP channel research platform Leuven, Department of Cellular and Molecular Medicine, University of Leuven, Leuven, Belgium.
Shawn M DavidsonKoch Institute for Integrative Cancer Research at Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Sandra SchoorsLaboratory of Angiogenesis and Neurovascular link, Department of Oncology, University of Leuven, Leuven, Belgium; Laboratory of Angiogenesis and Neurovascular link, Vesalius Research Center, VIB, Leuven, Belgium.
Dorien BroekaertLaboratory of Cellular Metabolism and Metabolic Regulation, Department of Oncology, University of Leuven, Leuven, Belgium; Laboratory of Cellular Metabolism and Metabolic Regulation, Vesalius Research Center, VIB, Leuven, Belgium.
Bert CruysLaboratory of Angiogenesis and Neurovascular link, Department of Oncology, University of Leuven, Leuven, Belgium; Laboratory of Angiogenesis and Neurovascular link, Vesalius Research Center, VIB, Leuven, Belgium.
Kristof GovaertsBiomedical MRI/Mosaic, Department of Imaging and Pathology, University of Leuven, Leuven, Belgium.
Carla De LegherLaboratory of Angiogenesis and Neurovascular link, Department of Oncology, University of Leuven, Leuven, Belgium; Laboratory of Angiogenesis and Neurovascular link, Vesalius Research Center, VIB, Leuven, Belgium.
Ann BouchéLaboratory of Angiogenesis and Neurovascular link, Department of Oncology, University of Leuven, Leuven, Belgium; Laboratory of Angiogenesis and Neurovascular link, Vesalius Research Center, VIB, Leuven, Belgium.
Luc SchoonjansLaboratory of Angiogenesis and Neurovascular link, Department of Oncology, University of Leuven, Leuven, Belgium; Laboratory of Angiogenesis and Neurovascular link, Vesalius Research Center, VIB, Leuven, Belgium.
Matt S RamerLaboratory of Angiogenesis and Neurovascular link, Department of Oncology, University of Leuven, Leuven, Belgium; Laboratory of Angiogenesis and Neurovascular link, Vesalius Research Center, VIB, Leuven, Belgium; International Collaboration on Repair Discoveries, the University of British Columbia, Vancouver, Canada.
Gene HungIsis Pharmaceuticals, Carlsbad, CA 92008, USA.
Goele BossaertLeuven Statistics Research Centre (LStat), University of Leuven, Leuven, Belgium.
Don W ClevelandLudwig Institute for Cancer Research, Department of Medicine and Neuroscience, University of California, San Diego, La Jolla, CA 92093, USA.
Uwe HimmelreichBiomedical MRI/Mosaic, Department of Imaging and Pathology, University of Leuven, Leuven, Belgium.
Thomas VoetsLaboratory of Ion Channel Research and TRP channel research platform Leuven, Department of Cellular and Molecular Medicine, University of Leuven, Leuven, Belgium.
Robin LemmensLaboratory of Neurobiology, Vesalius Research Center, VIB, Leuven, Belgium; Experimental Neurology (Department of Neurosciences) and Leuven Research Institute for Neuroscience and Disease (LIND), University of Leuven, Leuven, Belgium; Neurology, University Hospitals Leuven, Leuven, Belgium.
C Frank BennettIsis Pharmaceuticals, Carlsbad, CA 92008, USA.
Wim RobberechtLaboratory of Neurobiology, Vesalius Research Center, VIB, Leuven, Belgium; Experimental Neurology (Department of Neurosciences) and Leuven Research Institute for Neuroscience and Disease (LIND), University of Leuven, Leuven, Belgium; Neurology, University Hospitals Leuven, Leuven, Belgium.
Katrien De BockLaboratory of Angiogenesis and Neurovascular link, Department of Oncology, University of Leuven, Leuven, Belgium; Laboratory of Angiogenesis and Neurovascular link, Vesalius Research Center, VIB, Leuven, Belgium.
Mieke DewerchinLaboratory of Angiogenesis and Neurovascular link, Department of Oncology, University of Leuven, Leuven, Belgium; Laboratory of Angiogenesis and Neurovascular link, Vesalius Research Center, VIB, Leuven, Belgium.
Bart GhesquièreMetabolomics Expertise Center, Vesalius Research Center, VIB, Leuven, Belgium.
Sarah-Maria FendtLaboratory of Cellular Metabolism and Metabolic Regulation, Department of Oncology, University of Leuven, Leuven, Belgium; Laboratory of Cellular Metabolism and Metabolic Regulation, Vesalius Research Center, VIB, Leuven, Belgium.
Peter CarmelietLaboratory of Angiogenesis and Neurovascular link, Department of Oncology, University of Leuven, Leuven, Belgium; Laboratory of Angiogenesis and Neurovascular link, Vesalius Research Center, VIB, Leuven, Belgium. Electronic address: peter.carmeliet@vib-kuleuven.be.
KU Leuven · BEVIB-KU Leuven Center for Cancer Biology · BEIonis Pharmaceuticals (United States) · USLudwig Cancer Research · USMassachusetts Institute of Technology · USVIB-KU Leuven Center for Brain & Disease Research · BE
Funding
PRE-DOCTORAL TRAINING IN THE BIOLOGICAL SCIENCEST32GM007287 · NIGMS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI BELL, STEPHEN P., KEATING, AMY E · 1985 to 2019
$40.8MNEURONAL FILAMENT SYNTHESIS, ASSEMBLY, AND FUNCTIONR01NS027036 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Bogdan Bintu, Don W Cleveland · 1989 to 2026
$11.8MNIGMS NIH HHS T32 GM007287NINDS NIH HHS R01 NS027036
Abstract
The oxygen-sensing prolyl hydroxylase domain proteins (PHDs) regulate cellular metabolism, but their role in neuronal metabolism during stroke is unknown. Here we report that PHD1 deficiency provides neuroprotection in a murine model of permanent brain ischemia. This was not due to an increased collateral vessel network. Instead, PHD1(-/-) neurons were protected against oxygen-nutrient deprivation by reprogramming glucose metabolism. Indeed, PHD1(-/-) neurons enhanced glucose flux through the oxidative pentose phosphate pathway by diverting glucose away from glycolysis. As a result, PHD1(-/-) neurons increased their redox buffering capacity to scavenge oxygen radicals in ischemia. Intracerebroventricular injection of PHD1-antisense oligonucleotides reduced the cerebral infarct size and neurological deficits following stroke. These data identify PHD1 as a regulator of neuronal metabolism and a potential therapeutic target in ischemic stroke.
Indexed as
Cellular ReprogrammingGene DeletionAnimalsBrainBrain IschemiaCarbonFree Radical ScavengersHydroxylationHypoxia-Inducible Factor 1, alpha SubunitInjections, IntraventricularMice, KnockoutNeuronsNeuroprotectionOligonucleotidesOxidation-ReductionOxygenCarbonFree Radical ScavengersHif1a protein, mouseHypoxia-Inducible Factor 1, alpha SubunitOligonucleotidesOxygenPHD1 protein, mouseProcollagen-Proline DioxygenaseReactive Oxygen Species
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