title: Impact of the endoplasmic reticulum stress response in spinal cord after transient ischemia.
abstract: BACKGROUND
  Delayed paraplegia after operation of the thoracic aorta is considered to be related to vulnerability of motor neurons to ischemia. Recently, endoplasmic reticulum (ER) stress has been reported to participate in neuronal cell death. In the present study, we investigate the expression of ER stress-related molecules and discuss the relationship between neuronal vulnerability and ER stress after transient ischemia in the spinal cord.
  
  
  METHODS
  A rabbit spinal cord ischemia model was generated using a balloon catheter. In this model, spinal motor neurons show selectively delayed neuronal death whereas other spinal neuron, such as interneurons, survive. Immunohistochemical analysis and Western blotting for ER stress-related molecules, including phosphorylated eukaryotic initiation factor 2 alpha (p-eIF2alpha), activating transcription factor 4 (ATF4), glucose-regulated protein 78 (GRP78) and inositol-requiring ER transmembrane RNAse alpha isoform (IRE1alpha), were examined.
  
  
  RESULTS
  P-eIF2alpha, which inhibits protein synthesis and modulates ER stress, was induced only in interneurons after 6 h of reperfusion. ATF4, which is specifically activated by PERK-eIF2alpha, was induced only in interneurons between 6 h and 1 day after reperfusion. GRP78 was induced strongly both in interneurons and motor neurons at an early stage of reperfusion, but prolonged expression was observed only in interneurons. IRE1alpha, which is supposed to transduce an ER stress-related death signal, was expressed more strongly and over a more prolonged period in motor neurons.
  
  
  CONCLUSIONS
  These results indicate that the vulnerability of motor neurons in the spinal cord might be partially attributed to an ER stress response to transient ischemia.
authors: Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan. yamataka@surg1.med.osaka-u.ac.jp
authors: Takashi
authors: T
authors: Yamauchi
authors: Masahiro
authors: M
authors: Sakurai
authors: Koji
authors: K
authors: Abe
authors: Goro
authors: G
authors: Matsumiya
authors: Yoshiki
authors: Y
authors: Sawa
mesh_terms: D051701:Activating Transcription Factor 4 / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D016923:Cell Death / Q000502:physiology; D004195:Disease Models, Animal; D004721:Endoplasmic Reticulum / Q000378:metabolism / Q000473:pathology*; D000091342:Endoplasmic Reticulum Chaperone BiP; D004722:Endoribonucleases / Q000378:metabolism; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism; D005786:Gene Expression Regulation / Q000235:genetics; D006360:Heat-Shock Proteins / Q000378:metabolism; D007150:Immunohistochemistry; D007395:Interneurons / Q000378:metabolism / Q000473:pathology; D002546:Ischemic Attack, Transient / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D018832:Molecular Chaperones / Q000378:metabolism; D016472:Motor Neuron Disease / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D009046:Motor Neurons / Q000378:metabolism / Q000473:pathology*; D009410:Nerve Degeneration / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics; D018384:Oxidative Stress / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011817:Rabbits; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D020760:Spinal Cord Ischemia / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D015533:Transcriptional Activation / Q000235:genetics
chemical_list: D015415:Biomarkers; D000091342:Endoplasmic Reticulum Chaperone BiP; D015852:Eukaryotic Initiation Factor-2; C051684:GRP78 protein, rat; D006360:Heat-Shock Proteins; C000717248:Hspa5 protein, mouse; D018832:Molecular Chaperones; D009419:Nerve Tissue Proteins; D051701:Activating Transcription Factor 4; C510185:Ern1 protein, mouse; D017346:Protein Serine-Threonine Kinases; D004722:Endoribonucleases