Document Detail


CpG-ODN, the TLR9 agonist, attenuates myocardial ischemia/reperfusion injury: involving activation of PI3K/Akt signaling.
MedLine Citation:
PMID:  22917564     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Toll-like receptors (TLRs) have been implicated in myocardial ischemia/reperfusion (I/R) injury. The TLR9 ligand, CpG-ODN has been reported to improve cell survival. We examined effect of CpG-ODN on myocardial I/R injury.
METHODS: Male C57BL/6 mice were treated with either CpG-ODN, control-ODN, or inhibitory CpG-ODN (iCpG-ODN) 1h prior to myocardial ischemia (60min) followed by reperfusion. Untreated mice served as I/R control (n=10/each group). Infarct size was determined by TTC straining. Cardiac function was examined by echocardiography before and after myocardial I/R up to 14days.
RESULTS: CpG-ODN administration significantly decreased infarct size by 31.4% and improved cardiac function after myocardial I/R up to 14days. Neither control-ODN nor iCpG-ODN altered I/R-induced myocardial infarction and cardiac dysfunction. CpG-ODN attenuated I/R-induced myocardial apoptosis and prevented I/R-induced decrease in Bcl2 and increase in Bax levels in the myocardium. CpG-ODN increased Akt and GSK-3β phosphorylation in the myocardium. In vitro data suggested that CpG-ODN treatment induced TLR9 tyrosine phosphorylation and promoted an association between TLR9 and the p85 subunit of PI3K. Importantly, PI3K/Akt inhibition and Akt kinase deficiency abolished CpG-ODN-induced cardioprotection.
CONCLUSION: CpG-ODN, the TLR9 ligand, induces protection against myocardial I/R injury. The mechanisms involve activation of the PI3K/Akt signaling pathway.
Authors:
Zhijuan Cao; Danyang Ren; Tuanzhu Ha; Li Liu; Xiaohui Wang; John Kalbfleisch; Xiang Gao; Race Kao; David Williams; Chuanfu Li
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-08-16
Journal Detail:
Title:  Biochimica et biophysica acta     Volume:  1832     ISSN:  0006-3002     ISO Abbreviation:  Biochim. Biophys. Acta     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2012-12-10     Completed Date:  2013-03-04     Revised Date:  2014-01-09    
Medline Journal Info:
Nlm Unique ID:  0217513     Medline TA:  Biochim Biophys Acta     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  96-104     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier B.V. All rights reserved.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Line
Humans
Male
Mice
Mice, Inbred C57BL
Mice, Transgenic
Myocardial Ischemia / genetics,  metabolism,  surgery*
Oligodeoxyribonucleotides / administration & dosage*
Phosphatidylinositol 3-Kinases / genetics,  metabolism*
Proto-Oncogene Proteins c-akt / genetics,  metabolism*
Rats
Reperfusion Injury / drug therapy*,  genetics,  metabolism*
Signal Transduction / drug effects
Toll-Like Receptor 9 / agonists*,  genetics,  metabolism
Grant Support
ID/Acronym/Agency:
GM083016/GM/NIGMS NIH HHS; GM53552/GM/NIGMS NIH HHS; HL071837/HL/NHLBI NIH HHS; R01 GM083016/GM/NIGMS NIH HHS; R01 HL071837/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/CPG-oligonucleotide; 0/Oligodeoxyribonucleotides; 0/Tlr9 protein, mouse; 0/Toll-Like Receptor 9; EC 2.7.1.-/Phosphatidylinositol 3-Kinases; EC 2.7.11.1/Proto-Oncogene Proteins c-akt
Comments/Corrections

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