Spinal cord injury induces endoplasmic reticulum stress with different cell-type dependent response.
The mechanisms of injury-induced apoptosis of neurons within the spinal cord are poorly understood. In this study, we show that spinal cord injury (SCI) induces endoplasmic reticulum stress revealed by the activation of an unbalanced unfolded protein response (UPR). Using a weight-drop contusion model of SCI, the UPR activation was characterized by a quick transient phosphorylation of alpha subunit of eukaryotic initiation factor 2 soon restored by the up-regulation of its regulator Gadd34; an effective cleavage/activation of the ATF6alpha transcription factor leading to up-regulation of the canonical UPR target genes Chop, Xbp1 and Grp78; the presence of the processing of Xbp1 mRNA indicative of inositol requiring kinase 1 activation, and a gradual accumulation of C/EBP homologous transcription factor protein (CHOP) with concomitant caspase-12 activation. Interestingly, the subcellular distribution of CHOP was found in the nucleus of neurons and oligodendrocytes but in the cytoplasm of astrocytes. Considering the pro-apoptotic action attributed to this transcription factor, this phenomenon might account for the different susceptibility of cell types to dye after SCI.
Penas
Clara
C
Group of Neuroplasticity and Regeneration, Institute of Neurosciences and Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain.
Guzmán
Mónica-Sofía
MS
Verdú
Enrique
E
Forés
Joaquim
J
Navarro
Xavier
X
Casas
Caty
C
D051702:Activating Transcription Factor 6 / Q000378:metabolism; D000818:Animals; D050976:Basic-Leucine Zipper Transcription Factors / Q000378:metabolism; D001522:Behavior, Animal; D004268:DNA-Binding Proteins; D004721:Endoplasmic Reticulum / Q000473:pathology*; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000378:metabolism; D018832:Molecular Chaperones / Q000378:metabolism; D009043:Motor Activity / Q000502:physiology; D009363:Neoplasm Proteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D000071701:Regulatory Factor X Transcription Factors; D013119:Spinal Cord Injuries / Q000150:complications* / Q000473:pathology*; D013312:Stress, Physiological / Q000209:etiology* / Q000378:metabolism / Q000473:pathology*; D013997:Time Factors; D051742:Transcription Factor CHOP / Q000378:metabolism; D014157:Transcription Factors; D015854:Up-Regulation / Q000502:physiology; D000071717:X-Box Binding Protein 1; D000091342:Endoplasmic Reticulum Chaperone BiP
D051702:Activating Transcription Factor 6; D050976:Basic-Leucine Zipper Transcription Factors; D004268:DNA-Binding Proteins; D005904:Glial Fibrillary Acidic Protein; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D009363:Neoplasm Proteins; D000071701:Regulatory Factor X Transcription Factors; D051742:Transcription Factor CHOP; D014157:Transcription Factors; D000071717:X-Box Binding Protein 1; C497113:Atf6 protein, rat; C051684:GRP78 protein, rat; D000091342:Endoplasmic Reticulum Chaperone BiP; C000605545:Xbp1 protein, rat