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首页> 外文期刊>Brain injury: BI >Regulation of endoplasmic reticulum stress in rat cortex by p62/ZIP through the Keap1-Nrf2-ARE signalling pathway after transient focal cerebral ischaemia
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Regulation of endoplasmic reticulum stress in rat cortex by p62/ZIP through the Keap1-Nrf2-ARE signalling pathway after transient focal cerebral ischaemia

机译:p62 / ZIP通过短暂性局灶性脑缺血后Keap1-Nrf2-ARE信号通路对大鼠皮质内质网应激的调节

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Primary objective: p62/ZIP as the autophagy receptor can transport the misfolded proteins to a macroautophagy-lysosome system for degradation and also create a positive feedback loop between p62/ZIP and Nrf2. However, the role of p62/ZIP on cerebral ischaemia is unclear. The aim of this study was to evaluate the role of p62/ZIP in the regulation of endoplasmic reticulum(ER) stress induced by cerebral ischaemia/reperfusion. Research design: Different ischemic periods were designed by transient middle cerebral artery occlusion (tMCAO) using the suture method. Methods and procedures: At 24 hours after reperfusion, the ischaemic brain tissue was studied histologically and biochemically for autophagic, ER stress and Keap1-Nrf2-ARE signalling pathway markers. Main outcomes and results: Prolongation of ischaemia significantly increased the cortical injury observed in rats and was associated with a gradual increase in the protein expression of ubiquitin-aggregates, Grp78, GADD153/CHOP and p62/ZIP. Autophagy marker Atg12-Atg5 and LC3-PE increased and then decreased. Moreover, p62/ZIP mRNA expression increased and then decreased and was consistent with Nrf2 activation. Conclusions: p62/ZIP not only plays a key role in scavenging protein aggregates during autophagy, but it may also be involved in preventing oxidative injury and alleviating ER stress through the Keap1-Nrf2-ARE signalling pathway during cerebral ischaemia/reperfusion injury.
机译:主要目标:作为自噬受体的p62 / ZIP可以将错误折叠的蛋白质转运至自噬溶酶体系统进行降解,并在p62 / ZIP和Nrf2之间建立一个正反馈回路。但是,p62 / ZIP对脑缺血的作用尚不清楚。这项研究的目的是评估p62 / ZIP在调节脑缺血/再灌注诱导的内质网(ER)应激中的作用。研究设计:采用缝合法通过短暂性大脑中动脉闭塞(tMCAO)设计不同的缺血期。方法和步骤:在再灌注后24小时,组织学和生化研究缺血性脑组织的自噬,内质网应激和Keap1-Nrf2-ARE信号通路标记。主要结果和结果:缺血的延长显着增加了大鼠皮层损伤,并与泛素聚集体,Grp78,GADD153 / CHOP和p62 / ZIP的蛋白质表达逐渐增加有关。自噬标记Atg12-Atg5和LC3-PE先升高后降低。此外,p62 / ZIP mRNA表达先升高后降低,与Nrf2激活相一致。结论:p62 / ZIP不仅在自噬过程中清除蛋白聚集体中起关键作用,而且还可能通过Keap1-Nrf2-ARE信号通路通过预防脑缺血/再灌注损伤中的氧化损伤和减轻内质网应激。

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