Document Detail

Endoplasmic reticulum stress-dependent activation of ATF3 mediates the late phase of ischemic preconditioning.
MedLine Citation:
PMID:  25151953     Owner:  NLM     Status:  Publisher    
Ischemic preconditioning (PC) is an adaptive response to transient myocardial ischemia that protects the heart from subsequent ischemia/reperfusion (I/R) injury. However, the mechanisms underlying its cardioprotective effects remain unclear. Myocardium of adult male C57/BL6 mice, preconditioned by 6cycles of 4minute coronary occlusion and reperfusion, showed nuclear translocation of ATF3, and ATF6 and PERK phosphorylation 30min after PC. The abundance of ER proteins, ATF3 and ATF4 was increased 24h after PC; however, there was no evidence of IRE-1 activation in WT or ER-stress activated indicator (ERAI) mice expressing XBP-1-Venus fusion protein. PC-induced nuclear translocation of ATF3 was attenuated in transgenic mice with cardiac-restricted overexpression of inducible ATF6. Ischemic PC increased the abundance of inducible nitric oxide synthase, cyclooxygenase-2, heme oxygenase-1 and aldose reductase to levels similar between WT and ATF3-null hearts; however, the increase in IL-6 and ICAM-1 was exaggerated in ATF3-null hearts. Genetic deletion of ATF3 did not increase infarct size in non-preconditioned hearts but abolished the cardioprotective effects of PC. Larger infarct size in preconditioned ATF3-null hearts was associated with greater neutrophil infiltration in the myocardium, but no ATF3-dependent changes in the total or relative abundance of inflammatory monocytes were observed. Ischemic PC activates the unfolded protein response (UPR) and the activation of ATF3 by ER stress is essential for the cardioprotective effects of late PC.
Alan C Brooks; Mahavir Singh; Yiru Guo; James McCracken; Yu-Ting Xuan; Sanjay Srivastava; Roberto Bolli; Aruni Bhatnagar
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-8-22
Journal Detail:
Title:  Journal of molecular and cellular cardiology     Volume:  -     ISSN:  1095-8584     ISO Abbreviation:  J. Mol. Cell. Cardiol.     Publication Date:  2014 Aug 
Date Detail:
Created Date:  2014-8-26     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0262322     Medline TA:  J Mol Cell Cardiol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2014. Published by Elsevier Ltd.
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