1. Involvement of GPR30 in protection effect of Dexmedetomidine against myocardial ischemia/reperfusion injury in rat via AKT pathway
- Author
-
Huadong Ni, Xiaomin Hou, Qihong Shen, Zheming Shao, and Min Kong
- Subjects
Agonist ,Male ,Cardiotonic Agents ,medicine.drug_class ,Cell Survival ,Morpholines ,Myocardial Infarction ,Apoptosis ,Myocardial Reperfusion Injury ,Pharmacology ,Transfection ,General Biochemistry, Genetics and Molecular Biology ,Receptors, G-Protein-Coupled ,Rats, Sprague-Dawley ,chemistry.chemical_compound ,polycyclic compounds ,medicine ,Animals ,LY294002 ,Myocytes, Cardiac ,Protein kinase B ,PI3K/AKT/mTOR pathway ,Cells, Cultured ,Akt/PKB signaling pathway ,business.industry ,Drug Synergism ,Hypoxia (medical) ,medicine.disease ,Rats ,Disease Models, Animal ,chemistry ,Chromones ,Gene Knockdown Techniques ,Quinolines ,medicine.symptom ,business ,Reperfusion injury ,Proto-Oncogene Proteins c-akt ,hormones, hormone substitutes, and hormone antagonists ,Dexmedetomidine ,Signal Transduction - Abstract
Acute myocardial infarction (AMI) is a heart disease that seriously threatens human health. Dexmedetomidine (DEX) has a certain protective effect on cardiac injury. This study investigated the cardioprotective effect of DEX and its potential molecular mechanism in vivo and in vitro. The results showed that DEX could significantly increase the viability of hypoxia/reoxygenation (H/R) treated cardiomyocytes and reduce oxidative damage and apoptosis. Further molecular mechanism analysis showed that the above cardiac protective effects may be related to Akt signaling pathway. In addition, the expression of G-Protein Receptor 30 (GPR30) was promoted after H/R treatment. However, knockdown of GPR30 by shRNA significantly counteracted the cardioprotective effect of DEX. Meanwhile, we constructed a rat model of AMI to investigate the role of GPR30 in vivo. The results showed that DEX significantly reduced the infarct size, and GPR30 agonist G1 enhanced the protective effect of DEX on heart. On the contrary, protein kinase B (AKT) inhibitor LY294002 counteracted the protective effect of DEX on heart, suggesting that GPR30 enhanced the protective effect of DEX on ischemia-reperfusion induced heart injury by regulating AKT related pathways. In conclusion, our study provides a potential target for the clinical treatment of AMI.
- Published
- 2020