Title: Deletion or Inhibition of the Oxygen Sensor PHD1 Protects against Ischemic Stroke via Reprogramming of Neuronal Metabolism
Authors: Quaegebeur, Annelies
Segura, Inmaculada
Schmieder, Roberta
Verdegem, Dries
Decimo, Ilaria
Bifari, Francesco
Dresselaers, Tom
Eelen, Guy
Ghosh, Debapriva
Davidson, Shawn M
Schoors, Sandra
Broekaert, dorien
Cruys, Bert
Govaerts, Kristof
De Legher, Carla
Bouché, Ann
Schoonjans, Luc
Ramer, Matt S
Hung, Gene
Bossaert, Goele
Cleveland, Don W
Himmelreich, Uwe
Voets, Thomas
Lemmens, Robin
Bennett, C Frank
Robberecht, Wim
De Bock, Katrien
Dewerchin, Mieke
Ghesquière, Bart
Fendt, Sarah-Maria
Carmeliet, Peter # ×
Issue Date: Jan-2016
Publisher: Cell Press
Series Title: Cell Metabolism vol:23 pages:280-291
Article number: S1550-4131(15)00622-1
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.
ISSN: 1550-4131
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory for Neurobiology (VIB-KU Leuven Center for Brain & Disease Research)
Laboratory of Angiogenesis and Vascular Metabolism (VIB-KU Leuven Centre for Cancer Biology) (+)
Biomedical MRI
Laboratory of Cellular Metabolism and Metabolic Regulation (VIB-KU Leuven Centre for Cancer Biology) (+)
Leuven Statistics Research Centre (LStat)
Laboratory of Ion Channel Research (VIB-KU Leuven Center for Brain & Disease Research)
Exercise Physiology Research Group
× corresponding author
# (joint) last author

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