title: Involvement of endoplasmic reticulum stress after middle cerebral artery occlusion in mice.
abstract: The endoplasmic reticulum (ER) plays an important role in ischemic neuronal cell death. ER stress-related markers [immunoglobulin binding protein (BiP)/glucose-regulated protein (GRP) 78, activating transcription factor-4 (ATF-4), and C/EBP-homologous protein (CHOP)] in the striatum and the cortex were investigated after permanent middle cerebral artery occlusion (MCAO) in mice. Using endoplasmic reticulum stress-activated indicator (ERAI) transgenic mice, which show splicing of X-box protein 1 (XBP-1) mRNA as green fluorescence, we monitored the regional changes in fluorescence after MCAO. BiP mRNA (by reverse-transcription polymerase chain reaction [RT-PCR] analysis) was increased in the cortex at 6 h. In immunohistochemical and/or Western blot analysis, the expressions of ER stress-related markers (BiP, ATF-4, and CHOP) were increased in the infarct region, more strongly in the cortex than in the striatum. ERAI fluorescence was observed in the ischemic area starting from 6 and 12 h, respectively, after MCAO, with the peaks at 1 day and the fluorescence co-localized with the 2,3,5-triphenyltetrazolium chloride (TTC)-visible extension of brain infarction. These findings suggest that permanent MCAO induces expression of ER-stress related genes mainly in the periphery of the MCA territory.
authors.affiliation: Department of Biofunctional Molecules, Gifu Pharmaceutical University, 5-6-1 Mitahora-higashi, Gifu 502-8585, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Morimoto
authors.forename: Y
authors.initials: Y
authors.lastname: Oida
authors.forename: M
authors.initials: M
authors.lastname: Shimazawa
authors.forename: M
authors.initials: M
authors.lastname: Miura
authors.forename: T
authors.initials: T
authors.lastname: Kudo
authors.forename: K
authors.initials: K
authors.lastname: Imaizumi
authors.forename: H
authors.initials: H
authors.lastname: Hara
mesh_terms: D051701:Activating Transcription Factor 4 / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D000091342:Endoplasmic Reticulum Chaperone BiP; D007839:Functional Laterality; D005786:Gene Expression Regulation / Q000502:physiology*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000378:metabolism; D020244:Infarction, Middle Cerebral Artery / Q000473:pathology* / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018832:Molecular Chaperones / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D000071701:Regulatory Factor X Transcription Factors; D013312:Stress, Physiological / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D013997:Time Factors; D051742:Transcription Factor CHOP / Q000378:metabolism; D014157:Transcription Factors; D000071717:X-Box Binding Protein 1
chemical_list: C081452:Atf4 protein, mouse; D004268:DNA-Binding Proteins; D000091342:Endoplasmic Reticulum Chaperone BiP; D005904:Glial Fibrillary Acidic Protein; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D009687:Nuclear Proteins; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors; D000071717:X-Box Binding Protein 1; C000605544:Xbp1 protein, mouse; D051701:Activating Transcription Factor 4; D051742:Transcription Factor CHOP