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Article

ATP-sensitive K+ channels contribute to the protective effects of exogenous hydrogen sulfide against high glucose-induced injury in H9c2 cardiac cells

  • Authors:
    • Weijie Liang
    • Jingfu Chen
    • Liqiu Mo
    • Xiao Ke
    • Wenzhu Zhang
    • Dongdan Zheng
    • Wanying Pan
    • Shaoyun Wu
    • Jianqiang Feng
    • Mingcai Song
    • Xinxue Liao
  • View Affiliations / Copyright

    Affiliations: Department of Cardiology, Central Hospital of Panyu District, Guangzhou, Guangdong 511400, P.R. China, Department of Cardiac Care Unit, Huangpu Division of The First Affiliated Hospital, Sun Yat‑sen University, Guangzhou, Guangdong 510080, P.R. China, Department of Anesthesiology, Huangpu Division of The First Affiliated Hospital, Sun Yat‑sen University, Guangzhou, Guangdong 510080, P.R. China, Department of Cardiology, Sun Yat-sen Memorial Hospital, Sun Yat‑sen University, Guangzhou, Guangdong 510080, P.R. China, Department of Cardiac Catheterization, The First Affiliated Hospital, Sun Yat‑sen University, P.R. China, Department of Cardiology, The First Affiliated Hospital, Sun Yat-sun University, Guangzhou, Guangdong 510080, P.R. China
  • Pages: 763-772
    |
    Published online on: January 25, 2016
       https://doi.org/10.3892/ijmm.2016.2467
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Abstract

Hyperglycemia, as well as diabetes mellitus, has been shown to impair ATP-sensitive K+ (KATP) channels in human vascular smooth muscle cells. Hydrogen sulfide (H2S) is also known to be an opener of KATP channels. We previously demonstrated the cardioprotective effects exerted by H2S against high-glucose (HG, 35 mM glucose)-induced injury in H9c2 cardiac cells. As such, we hypothesized that KATP channels play a role in the cardioprotective effects of H2S against HG-induced injury. In this study, to examine this hypothesis, H9c2 cardiac cells were treated with HG for 24 h to establish a model of HG-induced insults. Our findings revealed that treatment of the cells with HG markedly decreased the expression level of KATP channels. However, the decreased expression of KATP channels was reversed by the treatment of the cells with 400 µM sodium hydrogen sulfide (NaHS, a donor of H2S) for 30 min prior to exposure to HG. Additionally, the HG-induced cardiomyocyte injuries, including cytotoxicity, apoptosis, oxidative stress and mitochondrial damage, were ameliorated by treatment with NaHS or 100 µM diazoxide (a mitochondrial KATP channel opener) or 50 µM pinacidil (a non-selective KATP channel opener) for 30 min prior to exposure to HG, as indicated by an increase in cell viability, as well as a decrease in the number of apoptotic cells, the expression of cleaved caspase-3, the generation of reactive oxygen species (ROS) and the dissipation of mitochondrial membrane potential (MMP). Notably, treatment of the H9c2 cardiac cells with 100 µM 5-hydroxydecanoic acid (5-HD, a mitochondrial KATP channel blocker) or 1 mM glibenclamide (Gli, a non-selective KATP channel blocker) for 30 min prior to treatment with NaHS and exposure to HG significantly attenuated the above-mentioned cardioprotective effects exerted by NaHS. Notably, treatment of the cells with 500 µM N-acetyl‑L‑cysteine (NAC, a scavenger of ROS) for 60 min prior to exposure to HG markedly reduced the HG-induced inhibitory effect on the expression of KATP channels. Taken together, our results suggest that KATP channels play an important role in the cardioprotective effects of exogenous H2S against HG-induced injury. This study also provides novel data demonstraring that there is an antagonistic interaction between ROS and KATP channels in HG-exposed H9c2 cardiac cells.
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Copy and paste a formatted citation
Spandidos Publications style
Liang W, Chen J, Mo L, Ke X, Zhang W, Zheng D, Pan W, Wu S, Feng J, Song M, Song M, et al: ATP-sensitive K+ channels contribute to the protective effects of exogenous hydrogen sulfide against high glucose-induced injury in H9c2 cardiac cells. Int J Mol Med 37: 763-772, 2016.
APA
Liang, W., Chen, J., Mo, L., Ke, X., Zhang, W., Zheng, D. ... Liao, X. (2016). ATP-sensitive K+ channels contribute to the protective effects of exogenous hydrogen sulfide against high glucose-induced injury in H9c2 cardiac cells. International Journal of Molecular Medicine, 37, 763-772. https://doi.org/10.3892/ijmm.2016.2467
MLA
Liang, W., Chen, J., Mo, L., Ke, X., Zhang, W., Zheng, D., Pan, W., Wu, S., Feng, J., Song, M., Liao, X."ATP-sensitive K+ channels contribute to the protective effects of exogenous hydrogen sulfide against high glucose-induced injury in H9c2 cardiac cells". International Journal of Molecular Medicine 37.3 (2016): 763-772.
Chicago
Liang, W., Chen, J., Mo, L., Ke, X., Zhang, W., Zheng, D., Pan, W., Wu, S., Feng, J., Song, M., Liao, X."ATP-sensitive K+ channels contribute to the protective effects of exogenous hydrogen sulfide against high glucose-induced injury in H9c2 cardiac cells". International Journal of Molecular Medicine 37, no. 3 (2016): 763-772. https://doi.org/10.3892/ijmm.2016.2467
Copy and paste a formatted citation
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Spandidos Publications style
Liang W, Chen J, Mo L, Ke X, Zhang W, Zheng D, Pan W, Wu S, Feng J, Song M, Song M, et al: ATP-sensitive K+ channels contribute to the protective effects of exogenous hydrogen sulfide against high glucose-induced injury in H9c2 cardiac cells. Int J Mol Med 37: 763-772, 2016.
APA
Liang, W., Chen, J., Mo, L., Ke, X., Zhang, W., Zheng, D. ... Liao, X. (2016). ATP-sensitive K+ channels contribute to the protective effects of exogenous hydrogen sulfide against high glucose-induced injury in H9c2 cardiac cells. International Journal of Molecular Medicine, 37, 763-772. https://doi.org/10.3892/ijmm.2016.2467
MLA
Liang, W., Chen, J., Mo, L., Ke, X., Zhang, W., Zheng, D., Pan, W., Wu, S., Feng, J., Song, M., Liao, X."ATP-sensitive K+ channels contribute to the protective effects of exogenous hydrogen sulfide against high glucose-induced injury in H9c2 cardiac cells". International Journal of Molecular Medicine 37.3 (2016): 763-772.
Chicago
Liang, W., Chen, J., Mo, L., Ke, X., Zhang, W., Zheng, D., Pan, W., Wu, S., Feng, J., Song, M., Liao, X."ATP-sensitive K+ channels contribute to the protective effects of exogenous hydrogen sulfide against high glucose-induced injury in H9c2 cardiac cells". International Journal of Molecular Medicine 37, no. 3 (2016): 763-772. https://doi.org/10.3892/ijmm.2016.2467
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