摘要 : Background: This study intends to investigate the potential involvement of E3 ubiquitin ligase COP1 in cerebral ischemia-reperfusion (I/R) injury.Methods: A mouse model of middle cerebral artery occlusion/reperfusion (MCAO/R) was ... 展开 Background: This study intends to investigate the potential involvement of E3 ubiquitin ligase COP1 in cerebral ischemia-reperfusion (I/R) injury.Methods: A mouse model of middle cerebral artery occlusion/reperfusion (MCAO/R) was established, and the ischemic penumbra of mouse brain cortex was collected and subjected to RNA-sequencing (RNA-seq). Primary glial cells, neurons and astrocytes were isolated, and microglia were exposed to oxygen and glucose deprivation/ reperfusion (OGD/R).Results: COP1 was poorly expressed in MCAO mice and OGD/R microglia. Restoration of COP1 suppressed the activation of microglia and relieves neuroinflammation in cerebral I/R injury, leading to alleviated brain damage (infraction volume [%]: [31.58 +/- 2.96] & [12.06 +/- 1.29], neurological scores: [3.6 +/- 0.6] & [1.2 +/- 0.5]). COP1 promoted the ubiquitin-mediated degradation of C/EBP beta in microglia. It was further revealed that COP1 attenuated microglia activation and phagocytosis (Iba + cells [N/mm2]: 182.68 +/- 20.89 & 84.57 +/- 12.08; soma area [mu m2]: 78.24 +/- 8.75 & 59.78 +/- 7.61) through negative regulation of C/EBP beta protein expression. Restoration of C/EBP beta negated the neuroprotective effects of COP1 in vivo. Discussion: This study illuminated a mechanism by which COP1 conferred a neuroprotective role in cerebral I/R injury via enhancing the ubiquitin-mediated degradation of transcriptional factor C/EBP beta in microglia. 收起