| 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 |
Related Documents
:
|
22907424 - The medical management of pediatric arrhythmias. 12869174 - Doxorubicin-induced canine chf: advantages and disadvantages. 21971524 - Mesenchymal stem cell transplantation for the infarcted heart: a role in minimizing abn... 7439234 - Protective effect of mercurascan after coronary artery ligation in the dog. 18805264 - Elevated preoperative hemoglobin a1c level is predictive of adverse events after corona... 22196944 - Cardiovascular magnetic resonance and single-photon emission computed tomography for di... |
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: 2013-04-16 |
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. |
Affiliation:
|
Department of Surgery, East Tennessee State University, Johnson City, TN 37614, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| 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 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Autophagy-dependent and -independent involvement of AMP-activated protein kinase in 6-hydroxydopamin...
Next Document: PPAR? ligand treatment inhibits cardiac inflammatory mediators induced by infection with different l...