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Article

Danshensu protects against ischemia/reperfusion injury and inhibits the apoptosis of H9c2 cells by reducing the calcium overload through the p-JNK-NF-κB-TRPC6 pathway

  • Authors:
    • Ying Meng
    • Wei-Zhu Li
    • You-Wei Shi
    • Bing-Feng Zhou
    • Rong Ma
    • Wei-Ping Li
  • View Affiliations / Copyright

    Affiliations: Department of Pharmacology, Key Laboratory of Anti-inflammatory and Immunopharmacology, Ministry of Education, Anhui Medical University, Hefei, Anhui 230032, P.R. China, Department of Cardiovascular Medicine, Binhu Hospital of Hefei City, Hefei, Anhui 230011, P.R. China, Department of Integrative Physiology and Cardiovascular Research Institute, University of North Texas Health Science Center, Fort Worth, TX 76107, USA
  • Pages: 258-266
    |
    Published online on: November 25, 2015
       https://doi.org/10.3892/ijmm.2015.2419
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Abstract

Ischemia-reperfusion (I/R) plays an important role in myocardial injury. In the present study, we aimed to examine the protective effects of Danshensu (DSS) against I/R injury and to elucidate the underlying mechanisms. For this purpose, H9c2 cells were cultured in hypoxic solution in a hypoxic incubator for 2 h, and then cultured in a high oxygen incubator for various periods of time and pre-treated with or without DSS, ammonium pyrrolidine dithiocarbamate (PDTC) or SP600125 [a c-Jun N-terminal kinase (JNK) inhibitor]. Cell apoptosis and cytosolic free Ca2+ ([Ca2+]i) levels were analyzed by flow cytometry. The protein expression levels of JNK, phosphorylated (p-)JNK, nuclear factor-κB (NF-κB) and transient receptor potential cation channel, subfamily C, member 6 (TRPC6) were measured by western blot analysis. The mRNA expression levels of JNK were measured by RT-qPCR. The results revealed that TRPC6 protein expression, the cell apoptotic rate and the [Ca2+]i levels increased in a time-dependent manner in the H9c2 cells following the induction of I/R injury. The apoptotic rate and TRPC6 protein expression decreased when the cells were treated with DSS prior to the induction of I/R injury. The knockdown of JNK expression by siRNA decreased the p-JNK and TRPC6 protein expression levels in the H9c2 cells subjected to I/R injury. The protein expression levels of p-JNK and NF-κB in the nucleus increased significantly when the H9c2 cells were subjected to I/R injury, whereas NF-κB expression in the cytoplasm decreased in a time‑dependent manner. However, p-JNK, NF-κB and TRPC6 protein expression, the [Ca2+]i level and cell apoptosis decreased when the H9c2 cells were pre-treated with DSS or SP600125. Therefore, our data suggest that DSS prevents myocardial I/R injury by inhibiting p-JNK activation and NF-κB translocation, which potentially upregulate TRPC6 expression, increase the [Ca2+]i level, and result in the apoptosis of H9c2 cells.
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Copy and paste a formatted citation
Spandidos Publications style
Meng Y, Li W, Shi Y, Zhou B, Ma R and Li W: Danshensu protects against ischemia/reperfusion injury and inhibits the apoptosis of H9c2 cells by reducing the calcium overload through the p-JNK-NF-κB-TRPC6 pathway. Int J Mol Med 37: 258-266, 2016.
APA
Meng, Y., Li, W., Shi, Y., Zhou, B., Ma, R., & Li, W. (2016). Danshensu protects against ischemia/reperfusion injury and inhibits the apoptosis of H9c2 cells by reducing the calcium overload through the p-JNK-NF-κB-TRPC6 pathway. International Journal of Molecular Medicine, 37, 258-266. https://doi.org/10.3892/ijmm.2015.2419
MLA
Meng, Y., Li, W., Shi, Y., Zhou, B., Ma, R., Li, W."Danshensu protects against ischemia/reperfusion injury and inhibits the apoptosis of H9c2 cells by reducing the calcium overload through the p-JNK-NF-κB-TRPC6 pathway". International Journal of Molecular Medicine 37.1 (2016): 258-266.
Chicago
Meng, Y., Li, W., Shi, Y., Zhou, B., Ma, R., Li, W."Danshensu protects against ischemia/reperfusion injury and inhibits the apoptosis of H9c2 cells by reducing the calcium overload through the p-JNK-NF-κB-TRPC6 pathway". International Journal of Molecular Medicine 37, no. 1 (2016): 258-266. https://doi.org/10.3892/ijmm.2015.2419
Copy and paste a formatted citation
x
Spandidos Publications style
Meng Y, Li W, Shi Y, Zhou B, Ma R and Li W: Danshensu protects against ischemia/reperfusion injury and inhibits the apoptosis of H9c2 cells by reducing the calcium overload through the p-JNK-NF-κB-TRPC6 pathway. Int J Mol Med 37: 258-266, 2016.
APA
Meng, Y., Li, W., Shi, Y., Zhou, B., Ma, R., & Li, W. (2016). Danshensu protects against ischemia/reperfusion injury and inhibits the apoptosis of H9c2 cells by reducing the calcium overload through the p-JNK-NF-κB-TRPC6 pathway. International Journal of Molecular Medicine, 37, 258-266. https://doi.org/10.3892/ijmm.2015.2419
MLA
Meng, Y., Li, W., Shi, Y., Zhou, B., Ma, R., Li, W."Danshensu protects against ischemia/reperfusion injury and inhibits the apoptosis of H9c2 cells by reducing the calcium overload through the p-JNK-NF-κB-TRPC6 pathway". International Journal of Molecular Medicine 37.1 (2016): 258-266.
Chicago
Meng, Y., Li, W., Shi, Y., Zhou, B., Ma, R., Li, W."Danshensu protects against ischemia/reperfusion injury and inhibits the apoptosis of H9c2 cells by reducing the calcium overload through the p-JNK-NF-κB-TRPC6 pathway". International Journal of Molecular Medicine 37, no. 1 (2016): 258-266. https://doi.org/10.3892/ijmm.2015.2419
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