title: Protective effects of XBP1 against oxygen and glucose deprivation/reoxygenation injury in rat primary hippocampal neurons.
abstract: The accumulation of misfolded and unfolded proteins in the endoplasmic reticulum (ER) induces ER stress, activating the unfolded protein response (UPR). One of the effectors of the UPR is XBP1, a critical transcriptional factor for genes responsible for cell survival. ER stress is also known to play a vital role in mediating ischemic reperfusion damage in the brain. In this study, we investigated the role of XBP1 in rat primary hippocampal neurons subjected to oxygen and glucose deprivation followed by reoxygenation (OGD/R) stress, an in vitro model of ischemia/reperfusion (I/R) injury. Primary neurons subjected to OGD had increased levels of spliced XBP1 (XBP1s) mRNA. Interestingly, the level of XBP1s decreased during the initial reoxygenation stress period. The combination of OGD and the subsequent 20-h reoxygenation stress period significantly increased the apoptotic death of primary cells. Overexpression of XBP1s suppressed cell death induced by OGD/R stress. These results suggest that suppression of XBP1 activation accelerates neuronal cell death after I/R and that activation of the XBP1 pathway may provide a therapeutic approach for the treatment of cerebral I/R injury.
authors.affiliation: Qs' Research Institute, Otsuka Pharmaceutical Co. Ltd., 463-10 Kagasuno, Kawauchi, Tokushima 771-0192, Japan.
authors.forename: Tatsuki
authors.initials: T
authors.lastname: Ibuki
authors.forename: Yuki
authors.initials: Y
authors.lastname: Yamasaki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Mizuguchi
authors.forename: Masahiro
authors.initials: M
authors.lastname: Sokabe
mesh_terms: D000818:Animals; D016923:Cell Death; D015687:Cell Hypoxia / Q000235:genetics; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D010084:Oxidation-Reduction; D010100:Oxygen / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D000071717:X-Box Binding Protein 1
chemical_list: D004268:DNA-Binding Proteins; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors; D000071717:X-Box Binding Protein 1; C000605545:Xbp1 protein, rat; D005947:Glucose; D010100:Oxygen