Open Access

Hydrosulfide attenuates acute myocardial ischemic injury through the glycogen synthase kinase-3β/β-catenin signaling pathway

  • Authors:
    • Ning Ge
    • Chao Liu
    • Guofeng Li
    • Lijun Xie
    • Qinzeng Zhang
    • Liping Li
    • Na Hao
    • Jianxin Zhang
  • View Affiliations

  • Published online on: March 24, 2016     https://doi.org/10.3892/ijmm.2016.2538
  • Pages: 1281-1289
  • Copyright: © Ge et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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.
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May-2016
Volume 37 Issue 5

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Ge N, Liu C, Li G, Xie L, Zhang Q, Li L, Hao N and Zhang J: Hydrosulfide attenuates acute myocardial ischemic injury through the glycogen synthase kinase-3β/β-catenin signaling pathway. Int J Mol Med 37: 1281-1289, 2016.
APA
Ge, N., Liu, C., Li, G., Xie, L., Zhang, Q., Li, L. ... Zhang, J. (2016). Hydrosulfide attenuates acute myocardial ischemic injury through the glycogen synthase kinase-3β/β-catenin signaling pathway. International Journal of Molecular Medicine, 37, 1281-1289. https://doi.org/10.3892/ijmm.2016.2538
MLA
Ge, N., Liu, C., Li, G., Xie, L., Zhang, Q., Li, L., Hao, N., Zhang, J."Hydrosulfide attenuates acute myocardial ischemic injury through the glycogen synthase kinase-3β/β-catenin signaling pathway". International Journal of Molecular Medicine 37.5 (2016): 1281-1289.
Chicago
Ge, N., Liu, C., Li, G., Xie, L., Zhang, Q., Li, L., Hao, N., Zhang, J."Hydrosulfide attenuates acute myocardial ischemic injury through the glycogen synthase kinase-3β/β-catenin signaling pathway". International Journal of Molecular Medicine 37, no. 5 (2016): 1281-1289. https://doi.org/10.3892/ijmm.2016.2538