Spinal cord injury induces endoplasmic reticulum stress with different cell-type dependent response.

Abstract:

: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.

journal_name

J Neurochem

authors

Penas C,Guzmán MS,Verdú E,Forés J,Navarro X,Casas C

doi

10.1111/j.1471-4159.2007.04671.x

subject

Has Abstract

pub_date

2007-08-01 00:00:00

pages

1242-55

issue

4

eissn

0022-3042

issn

1471-4159

pii

JNC4671

journal_volume

102

pub_type

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