| First Author | Quaegebeur A | Year | 2016 |
| Journal | Cell Metab | Volume | 23 |
| Issue | 2 | Pages | 280-91 |
| PubMed ID | 26774962 | Mgi Jnum | J:232857 |
| Mgi Id | MGI:5780351 | Doi | 10.1016/j.cmet.2015.12.007 |
| Citation | Quaegebeur A, et al. (2016) Deletion or Inhibition of the Oxygen Sensor PHD1 Protects against Ischemic Stroke via Reprogramming of Neuronal Metabolism. Cell Metab 23(2):280-91 |
| abstractText | 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. |
