| First Author | He C | Year | 2022 |
| Journal | Int J Biol Macromol | Volume | 222 |
| Issue | Pt B | Pages | 1789-1800 |
| PubMed ID | 36191790 | Mgi Jnum | J:372942 |
| Mgi Id | MGI:8250642 | Doi | 10.1016/j.ijbiomac.2022.09.264 |
| Citation | He C, et al. (2022) E3 ubiquitin ligase COP1 confers neuroprotection in cerebral ischemia/reperfusion injury via regulation of transcription factor C/EBPbeta in microglia. Int J Biol Macromol 222(Pt B):1789-1800 |
| abstractText | 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/EBPbeta in microglia. It was further revealed that COP1 attenuated microglia activation and phagocytosis (Iba+cells [N/mm(2)]: 182.68+/-20.89 & 84.57+/-12.08; soma area [mum(2)]: 78.24+/-8.75 & 59.78+/-7.61) through negative regulation of C/EBPbeta protein expression. Restoration of C/EBPbetanegated 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/EBPbeta in microglia. |
