title: Induction of murine HRD1 in experimental cerebral ischemia.
abstract: Hrd1p in yeast plays an important role in endoplasmic reticulum-associated degradation (ERAD). In the present study, we used an in vivo model of hypoxia-ischemia in mice to study the expression of murine HRD1. Hypoxia-ischemia induced a significant increase in mRNA levels of genes including GRP78, CHOP and MyD116, the expression of which are specifically activated under conditions associated with ER dysfunction. The level of mHRD1 mRNA was significantly increased after ischemia. Interestingly, induction of mHRD1 was elevated at a later time point (12-48 h) in the ischemic cortex, whereas it increased at an earlier time point (3-12 h) in the injured striatum. We also examined the changes of mHRD1 mRNA expression in neuroblastoma Neuro2a and primary glial cells exposed to hypoxia/reoxygenation. The expression of mHRD1 mRNA was remarkably up-regulated in glial cells subjected to 24 h hypoxia, whereas no significant changes were observed in Neuro2a cells under hypoxia/reoxygenation. In addition, the levels of mHRD1 mRNA were markedly elevated in glial cells exposed to treatment with tunicamycin (Tm, an ER stress inducer). These findings suggest that hypoxia-ischemia triggers ER dysfunction and mHRD1 may play a role in ischemia-induced ER dysfunction.
authors.affiliation: Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan.
authors.forename: Xin
authors.initials: X
authors.lastname: Qi
authors.forename: Yasunobu
authors.initials: Y
authors.lastname: Okuma
authors.forename: Toru
authors.initials: T
authors.lastname: Hosoi
authors.forename: Masayuki
authors.initials: M
authors.lastname: Kaneko
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Nomura
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000943:Antigens, Differentiation / Q000235:genetics / Q000378:metabolism; D000998:Antiviral Agents / Q000494:pharmacology; D001921:Brain / Q000473:pathology; D001929:Brain Edema / Q000209:etiology / Q000473:pathology; D020520:Brain Infarction / Q000209:etiology / Q000473:pathology; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D002478:Cells, Cultured; D004195:Disease Models, Animal; D000091342:Endoplasmic Reticulum Chaperone BiP; D007839:Functional Laterality; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006931:Hyperbaric Oxygenation / Q000379:methods; D020925:Hypoxia-Ischemia, Brain / Q000150:complications / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D020287:In Situ Nick-End Labeling / Q000379:methods; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D009447:Neuroblastoma / Q000378:metabolism; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D013778:Tetrazolium Salts; D013997:Time Factors; D051742:Transcription Factor CHOP; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014415:Tunicamycin / Q000494:pharmacology; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*; D054645:Protein Phosphatase 1
chemical_list: D000943:Antigens, Differentiation; D000998:Antiviral Agents; D022762:CCAAT-Enhancer-Binding Proteins; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D029701:Saccharomyces cerevisiae Proteins; D013778:Tetrazolium Salts; D051742:Transcription Factor CHOP; D014157:Transcription Factors; D014415:Tunicamycin; D044767:Ubiquitin-Protein Ligases; C497250:Ddit3 protein, mouse; C000717248:Hspa5 protein, mouse; C009591:triphenyltetrazolium; C104621:HRD1 protein, S cerevisiae; C498235:Syvn1 protein, mouse; C513256:Ppp1r15a protein, mouse; D054645:Protein Phosphatase 1