Relative Contribution of Prolyl Hydroxylase-Dependent and -Independent Degradation of HIF-1alpha by Proteasomal Pathways in Cerebral Ischemia.

ABSTRACT: Hypoxia inducible factor-1 (HIF-1) is a key regulator in hypoxia and can determine the fate of brain cells during ischemia. However, the mechanism of HIF-1 regulation is still not fully understood in ischemic brains. We tested a hypothesis that both the 26S and the 20S proteasomal pathways were involved in HIF-1α degradation under ischemic conditions. Using in vitro ischemic model (oxygen and glucose deprivation) and a mouse model of middle cerebral artery occlusion, we tested effects of inhibitors of proteasomes and prolyl hydroxylase (PHD) on HIF-1α stability and brain injury in cerebral ischemia. We observed that 30 and 60 min of oxygen-glucose deprivation significantly increased the 20S proteasomal activity. We demonstrated that proteasome inhibitors increased HIF-1α stabilizati

SUBMITTER: Badawi Y 

PROVIDER: S-EPMC5434458 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature