Hydrosulfide attenuates acute myocardial ischemic injury through the glycogen synthase kinase-3β/β-catenin signaling pathway
| Autor: | Jianxin Zhang, Li-Jun Xie, Na Hao, Qin-zeng Zhang, Ning Ge, Guofeng Li, Li-ping Li, Chao Liu |
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| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Male Mean arterial pressure Blood Pressure Myocardial Reperfusion Injury 030204 cardiovascular system & hematology Pharmacology Bioinformatics glycogen synthase kinase-3β 03 medical and health sciences Necrosis Ventricular Dysfunction Left 0302 clinical medicine Downregulation and upregulation GSK-3 Genetics medicine Animals Myocardial infarction Hydrogen Sulfide Phosphorylation Glycogen synthase GSK3B beta Catenin Glycogen Synthase Kinase 3 beta biology business.industry Myocardium apoptosis General Medicine Articles β-catenin medicine.disease Rats hydrosulfide Disease Models Animal 030104 developmental biology Apoptosis biology.protein Apoptotic signaling pathway SB216763 business acute myocardial ischemia Biomarkers Signal Transduction |
| Zdroj: | International Journal of Molecular Medicine |
| ISSN: | 1791-244X |
| Popis: | The endogenous signaling gasotransmitter, hydrosulfide (H2S), has been shown to exert cardioprotective effects against acute myocardial infarction (AMI) due to ischemic injury. However, the mechanisms responsible for these effects are not yet fully understood. In this study, we investigated whether sodium hydrogen sulfide (NaHS), an H2S donor, attenuates acute myocardial ischemic injury through glycogen synthase kinase-3β (GSK-3β)/β-catenin signaling. For this purpose, we utilized an in vivo rat model of AMI by occluding the left anterior descending coronary artery. NaHS (0.39, 0.78 or 1.56 mg/kg, intraperitoneally), the GSK-3β inhibitor, SB216763 (0.6 mg/kg, intravenously), or 1% dimethylsulfoxide (2 ml/kg, intravenously) were administered to the rats. The results demonstrated that the administration of medium- and high-dose NaHS and SB216763 significantly improved rat cardiac function, as evidenced by an increase in the mean arterial pressure, left ventricular developed pressure, contraction and relaxation rates, as well as a decrease in left ventricular end-diastolic pressure. In addition, the administration of NaHS and SB216763 attenuated myocardial injury as reflected by a decrease in apoptotic cell death and in the serum lactate dehydrogenase concentrations, and prevented myocardial structural changes. The administration of NaHS and SB216763 increased the concentrations of phosphorylated (p-)GSK-3β, the p-GSK-3β/t-GSK-3β ratio and downstream protein β-catenin. Moreover, western blot and immunohistochemical analyses of apoptotic signaling pathway proteins further established the cardioprotective potential of NaHS, as reflected by the upregulation of Bcl-2 expression, the downregulation of Bax expression, and a decrease in the number of TUNEL-positive stained cells. These findings suggest that hydrosulfide exerts cardioprotective effects against AMI-induced apoptosis through the GSK-3β/β-catenin signaling pathway. |
| Databáze: | OpenAIRE |
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