Neuroprotective Effect of E3 Ubiquitin Ligase RNF8 Against Ischemic Stroke via HDAC2 Stability Reduction and Reelin-Dependent GSK3β Inhibition.

ABSTRACT: Loss of E3 ubiquitin ligase RING finger protein 8 (RNF8) may lead to neuronal DNA damage and apoptosis. In order to expand on our knowledge on the mechanistic basis underlying neuronal death in ischemic stroke, the present study sought to investigate the potential role of E3 ubiquitin ligase RNF8 on ischemic stroke and explore the underlying downstream mechanism. Middle cerebral artery occlusion (MCAO) in mice and oxygen-glucose deprivation/reoxygenation (OGD/R) in neurons were induced to simulate an ischemic stroke environment. It was found that downregulation of RNF8 and Reelin occurred in MCAO mice and OGD/R-exposed neurons. Silencing of RNF8 enhanced the MCAO-induced neuronal apoptosis and oxidative stress. Mechanistically, RNF8 enhanced the ubiquitination and degradation of HDAC2, thu

SUBMITTER: Zhu X 

PROVIDER: S-EPMC9135995 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature