title: Hydrosulfide attenuates acute myocardial ischemic injury through the glycogen synthase kinase-3β/β-catenin signaling pathway.
abstract: 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.
authors.affiliation: Department of Pharmacology, Hebei Medical University, Shijiazhuang, Hebei 050021, P.R. China.
authors.forename: Ning
authors.initials: N
authors.lastname: Ge
authors.affiliation: Department of Pharmacology, Hebei Medical University, Shijiazhuang, Hebei 050021, P.R. China.
authors.forename: Chao
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Pharmacology, Hebei Academy of Medical Sciences, Shijiazhuang, Hebei 050021, P.R. China.
authors.forename: Guofeng
authors.initials: G
authors.lastname: Li
authors.affiliation: Department of Pharmacology, Hebei Academy of Medical Sciences, Shijiazhuang, Hebei 050021, P.R. China.
authors.forename: Lijun
authors.initials: L
authors.lastname: Xie
authors.affiliation: Department of Pharmacology, Hebei Academy of Medical Sciences, Shijiazhuang, Hebei 050021, P.R. China.
authors.forename: Qinzeng
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, Hebei Academy of Medical Sciences, Shijiazhuang, Hebei 050021, P.R. China.
authors.forename: Liping
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Pharmacology, Hebei Academy of Medical Sciences, Shijiazhuang, Hebei 050021, P.R. China.
authors.forename: Na
authors.initials: N
authors.lastname: Hao
authors.affiliation: Department of Pharmacology, Hebei Medical University, Shijiazhuang, Hebei 050021, P.R. China.
authors.forename: Jianxin
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015415:Biomarkers; D001794:Blood Pressure / Q000187:drug effects; D004195:Disease Models, Animal; D000071679:Glycogen Synthase Kinase 3 beta / Q000378:metabolism*; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D009336:Necrosis / Q000473:pathology; D010766:Phosphorylation; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects*; D018487:Ventricular Dysfunction, Left; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D051176:beta Catenin; D000071679:Glycogen Synthase Kinase 3 beta; D006862:Hydrogen Sulfide