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Effect of amiloride on endoplasmic reticulum stress response in the injured spinal cord of rats
Author(s) -
Kuroiwa Masahiro,
Watanabe Masahiko,
Katoh Hiroyuki,
Suyama Kaori,
Matsuyama Daisuke,
Imai Takeshi,
Mochida Joji
Publication year - 2014
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/ejn.12647
Subject(s) - amiloride , unfolded protein response , endoplasmic reticulum , medicine , chop , spinal cord , spinal cord injury , apoptosis , neuroprotection , endocrinology , pharmacology , chemistry , microbiology and biotechnology , biology , sodium , biochemistry , chemotherapy , organic chemistry , psychiatry
After traumatic spinal cord injury ( SCI ), endoplasmic reticulum ( ER ) stress exacerbates secondary injury, leading to expansion of demyelination and reduced remyelination due to oligodendrocyte precursor cell ( OPC ) apoptosis. Although recent studies have revealed that amiloride controls ER stress and leads to improvement in several neurological disorders including SCI , its mechanism is not completely understood. Here, we used a rat SCI model to assess the effects of amiloride on functional recovery, secondary damage expansion, ER stress‐induced cell death and OPC survival. Hindlimb function in rats with spinal cord contusion significantly improved after amiloride administration. Amiloride significantly decreased the expression of the pro‐apoptotic transcription factor CHOP in the injured spinal cord and significantly increased the expression of the ER chaperone GRP 78, which protects cells against ER stress. In addition, amiloride treatment led to a significant decrease in ER stress‐induced apoptosis and a significant increase of NG 2‐positive OPC s in the injured spinal cord. Furthermore, in vitro experiments performed to investigate the direct effect of amiloride on OPC s revealed that amiloride reduced CHOP expression in OPC s cultured under ER stress. These results suggest that amiloride controls ER stress in SCI and inhibits cellular apoptosis, contributing to OPC survival. The present study suggests that amiloride may be an effective treatment to reduce ER stress‐induced cell death in the acute phase of SCI .