Document Detail

Reduced Endoplasmic Reticulum Stress Might Alter the Course of Heart Failure Via Caspase-12 and JNK Pathways.
MedLine Citation:
PMID:  24565258     Owner:  NLM     Status:  In-Data-Review    
BACKGROUND: Endoplasmic reticulum (ER) stress plays an important role in mediating ischemic heart cell death. The aim of this study was to investigate whether manipulation of a key factor of the ER stress pathway, eukaryotic translation initiation factor 2 subunit α (eIF2α), can change the natural history of heart failure (HF).
METHODS: HF was induced using coronary artery ligation in adult rats and a selective eIF2α dephosphorylation inhibitor, salubrinal (Sal), was used. Thirty minutes after ligation, rats were randomly assigned to 3 groups: myocardial infarction (MI) plus placebo injections (dimethyl sulfoxide; n = 12), MI plus Sal injection (Sal; n = 12), and MI (HF; n = 12). Hemodynamic parameters were examined. Hearts were harvested for apoptosis assessment after 8 weeks of Sal treatment by terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labelling and flow cytometric analysis. Hearts were harvested to determine ER chaperones by Western analysis, real-time polymerase chain reaction and immunohistochemical analysis.
RESULTS: Cardiac function was significantly improved in Sal-treated rats. Apoptosis was reduced by Sal treatment. Glucose-regulated protein-78 and -94 were increased in HF but normalized by Sal treatment. HF caused a significant increase in eIF2α phosphorylation, which was further increased by Sal treatment, and caspase-12 and phospho-c-JUN NH2-terminal kinase were markedly increased in rats with HF alone but significantly reduced by Sal treatment.
CONCLUSIONS: Our results suggest that reduction of ER stress and myocardial apoptosis through inhibition of eIF2α dephosphorylation might alter the natural history of HF, which might provide a new approach for its treatment.
Yu Liu; Jie Wang; Shu-Ying Qi; Lei-Sheng Ru; Chao Ding; Hai-Jun Wang; Jing-Shan Zhao; Jing-Jing Li; Ai-Ying Li; Dong-Mei Wang
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Publication Detail:
Type:  Journal Article     Date:  2013-11-06
Journal Detail:
Title:  The Canadian journal of cardiology     Volume:  30     ISSN:  1916-7075     ISO Abbreviation:  Can J Cardiol     Publication Date:  2014 Mar 
Date Detail:
Created Date:  2014-02-25     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8510280     Medline TA:  Can J Cardiol     Country:  England    
Other Details:
Languages:  eng     Pagination:  368-75     Citation Subset:  IM    
Copyright Information:
Copyright © 2014 Canadian Cardiovascular Society. All rights reserved.
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