title: Regulation of endoplasmic reticulum stress in rat cortex by p62/ZIP through the Keap1-Nrf2-ARE signalling pathway after transient focal cerebral ischaemia.
abstract: 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.
  
  
  METHODS
  Different ischemic periods were designed by transient middle cerebral artery occlusion (tMCAO) using the suture method.
  
  
  METHODS
  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.
  
  
  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.
authors.affiliation: Department of Pathophysiology, Norman Bethune College of Medicine, Jilin University, 126 Xinmin Street, Changchun, Jilin, China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Wang
authors.forename: Jinsong
authors.initials: J
authors.lastname: Kang
authors.forename: Hongyan
authors.initials: H
authors.lastname: Li
authors.forename: Jing
authors.initials: J
authors.lastname: Su
authors.forename: Jiang
authors.initials: J
authors.lastname: Wu
authors.forename: Ye
authors.initials: Y
authors.lastname: Xu
authors.forename: Huimei
authors.initials: H
authors.lastname: Yu
authors.forename: Xiyan
authors.initials: X
authors.lastname: Xiang
authors.forename: Haowei
authors.initials: H
authors.lastname: Yi
authors.forename: Yuxiong
authors.initials: Y
authors.lastname: Lu
authors.forename: Liankun
authors.initials: L
authors.lastname: Sun
mesh_terms: D000818:Animals; D008297:Male; D051381:Rats; D001343:Autophagy; D015153:Blotting, Western; D001921:Brain / Q000098:blood supply / Q000378:metabolism; D002545:Brain Ischemia / Q000378:metabolism; D059865:Endoplasmic Reticulum Stress; D006360:Heat-Shock Proteins / Q000378:metabolism; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D000072019:Kelch-Like ECH-Associated Protein 1; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology; D000071456:Sequestosome-1 Protein; D015398:Signal Transduction; D013997:Time Factors; D051742:Transcription Factor CHOP / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D000091342:Endoplasmic Reticulum Chaperone BiP
chemical_list: D006360:Heat-Shock Proteins; D047908:Intracellular Signaling Peptides and Proteins; D000072019:Kelch-Like ECH-Associated Protein 1; D000071456:Sequestosome-1 Protein; D051742:Transcription Factor CHOP; D051267:NF-E2-Related Factor 2; C497251:Ddit3 protein, rat; C051684:GRP78 protein, rat; D000091342:Endoplasmic Reticulum Chaperone BiP; C486610:KEAP1 protein, rat; C491079:Sqstm1 protein, rat