Suppression of Long Non-Coding RNA LINC00652 Restores Sevoflurane-Induced Cardioprotection Against Myocardial Ischemia-Reperfusion Injury by Targeting GLP-1R Through the cAMP/PKA Pathway in Mice
| Autor: | Shu-Bo Zhang, Guo-Hua Pu, Xiao-Zeng Gao, Bao-Yong Li, Tie-Jun Liu, Xiao-Liang Han |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Cardiac function curve Male Methyl Ethers Glucagon-like peptide 1 receptor (GLP-1R) Physiology Interleukin-1beta Apoptosis Myocardial Reperfusion Injury Pharmacology CREB lcsh:Physiology Glucagon-Like Peptide-1 Receptor lcsh:Biochemistry 03 medical and health sciences Long-non-coding RNA LINC00652 Mice Sevoflurane Cyclic AMP Medicine Animals lcsh:QD415-436 Myocardial infarction RNA Small Interfering Cyclic AMP Response Element-Binding Protein 3' Untranslated Regions Cardioprotection biology lcsh:QP1-981 business.industry Kinase Myocardium Hemodynamics medicine.disease Adenosine Cyclic AMP-Dependent Protein Kinases Mice Inbred C57BL Disease Models Animal 030104 developmental biology biology.protein CAMP/PKA pathway RNA Interference RNA Long Noncoding Myocardial ischemia-reperfusion business Reperfusion injury medicine.drug Signal Transduction |
| Zdroj: | Cellular Physiology and Biochemistry, Vol 49, Iss 4, Pp 1476-1491 (2018) |
| ISSN: | 1421-9778 |
| Popis: | Background/Aims: Long non-coding RNA (lncRNA) and glucagon-like peptide 1 receptor (GLP-1R) are crucial for heart development and for adult heart structural maintenance and function. Herein, we performed a study to explore the effect of lncRNA LINC00652 (LINC00652) on myocardial ischemia-reperfusion (I/R) injury by targeting GLP-1R through the cyclic adenosine monophosphate-protein kinase A (cAMP/PKA) pathway. Methods: Bioinformatics software was used to screen the long-chain non-coding RNAs associated with myocardial ischemia-reperfusion and to predict target genes. The mRNA and protein levels of LINC00652, GLP-1R and CREB were detected by RT-qPCR and western blotting. In order to identify the interaction between LINC00652 and myocardial I/R injury, the cardiac function, the hemodynamic changes, the pathological changes of the myocardial tissues, the myocardial infarct size, and the apoptosis of myocardial cells of mice were measured. Meanwhile, the levels of serum IL-1β and TNF-α were detected. Results: LINC00652 was overexpressed in the myocardial cells of mice with myocardial I/R injury. GLP-1R is the target gene of LINC00652. We also determined higher levels of LINC00652 and GLP-1R in the I/R modeled mice. Additionally, si-LINC00652 decreased cardiac pathology, infarct size, apoptosis rates of myocardial cells, and levels of IL-1β and TNF-α, and increased GLP-1R expression cardiac function, normal hemodynamic index, and the expression and phosphorylation of GLP-1R and CREB proteins. Conclusion: Taken together, our key findings of the present highlight LINC00652 inhibits the activation of the cAMP/PKA pathway by targeting GLP-1R to reduce the protective effect of sevoflurane on myocardial I/R injury in mice. |
| Databáze: | OpenAIRE |
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