Chloroquine Promotes the Recovery of Acute Spinal Cord Injury by Inhibiting Autophagy-Associated Inflammation and Endoplasmic Reticulum Stress.
J Neurotrauma
; 35(12): 1329-1344, 2018 06 15.
Article
em En
| MEDLINE
| ID: mdl-29316847
ABSTRACT
Spinal cord injury (SCI) is a severe nervous system disease that may lead to lifelong disability. Studies have shown that autophagy plays a key role in various diseases; however, the mechanisms regulating cross-talk between autophagy, inflammation, and endoplasmic reticulum (ER) stress during SCI recovery remain unclear. This study was designed to investigate the mechanism by which chloroquine (CQ) inhibits autophagy-associated inflammation and ER stress in rats during their recovery from acute SCI. We evaluated the locomotor function, level of autophagy, and levels of inflammatory cytokines and ER-stress-associated proteins and examined the degradation of the key regulator of inflammation inhibitor of kappa B alpha (I-κBα) through autophagy by analyzing the colocalization of I-κBα, p62, and microtubule-associated protein 1 light chain 3-II. In addition, overexpression of the p62 and activating transcription factor 4 (ATF4) silencing plasmids was used to verify the important roles for autophagic degradation and ER stress. In this study, locomotor function is improved, and autophagy and inflammation are significantly inhibited by, CQ treatment in the model rats. In addition, CQ significantly inhibits the degradation of ubiquitinated I-κBα and blocks the nuclear translocation of nuclear factor kappa B p65 and expression of inflammatory factors. Overexpression of p62 increases I-κBα degradation and improves inflammatory responses. Moreover, CQ treatment also inhibits the activation of ER stress in the rat SCI model, and the ATF4 signaling pathway is required for ER-stress-induced activation of autophagy. These findings reveal a novel mechanism underlying the beneficial effects of CQ on the recovery of SCI, particularly the mechanisms regulating cross-talk between autophagy, inflammation, and ER stress.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Traumatismos da Medula Espinal
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Cloroquina
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Fármacos Neuroprotetores
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Estresse do Retículo Endoplasmático
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Inflamação
Tipo de estudo:
Prognostic_studies
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Risk_factors_studies
Limite:
Animals
Idioma:
En
Revista:
J Neurotrauma
Assunto da revista:
NEUROLOGIA
/
TRAUMATOLOGIA
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
China