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Tanshinone IIA confers protection against myocardial ischemia/reperfusion injury by inhibiting ferroptosis and apoptosis via VDAC1

  • Authors:
    • Tie Hu
    • Hua-Xi Zou
    • Shu-Yu Le
    • Ya-Ru Wang
    • Ya-Mei Qiao
    • Yong Yuan
    • Ji-Chun Liu
    • Song-Qing Lai
    • Huang Huang
  • View Affiliations / Copyright

    Affiliations: Institute of Cardiovascular Surgical Diseases, Jiangxi Academy of Clinical Medical Sciences, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China, Department of Cardiovascular Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China
    Copyright: © Hu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 109
    |
    Published online on: October 3, 2023
       https://doi.org/10.3892/ijmm.2023.5312
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Abstract

Tanshinone IIA (TSN) extracted from danshen (Salvia miltiorrhiza) could protect cardiomyocytes against myocardial ischemia/reperfusion injury (IRI), however the underlying molecular mechanisms of action remain unclear. The aim of the present study was to identify the protective effects of TSN and its mechanisms of action through in vitro studies. An anoxia/reoxygenation (A/R) injury model was established using H9c2 cells to simulate myocardial IRI in vitro. Before A/R, H9c2 cardiomyoblasts were pretreated with 8 µM TSN or 10 µM ferrostatin‑1 (Fer‑1) or erastin. The cell counting kit 8 (CCK‑8) and lactate dehydrogenase (LDH) assay kit were used to detect the cell viability and cytotoxicity. The levels of total iron, glutathione (GSH), glutathione disulfide (GSSG), malondialdehyde (MDA), ferrous iron, caspase‑3 activity, and reactive oxygen species (ROS) were assessed using commercial kit. The levels of mitochondrial membrane potential (MMP), lipid ROS, cell apoptosis, and mitochondrial permeability transition pore (mPTP) opening were detected by flow cytometry. Transmission electron microscopy (TEM) was used to observed the mitochondrial damage. Protein levels were detected by western blot analysis. The interaction between TSN and voltage‑dependent anion channel 1 (VDAC1) was evaluated by molecular docking simulation. The results showed that pretreatment with TSN and Fer‑1 significantly decreased cell viability, glutathione peroxidase 4 (GPX4) protein and GSH expression and GSH/GSSG ratio and inhibited upregulation of LDH activity, prostaglandin endoperoxide synthase 2 and VDAC1 protein expression, ROS levels, mitochondrial injury and GSSG induced by A/R. TSN also effectively inhibited the damaging effects of erastin treatment. Additionally, TSN increased MMP and Bcl‑2/Bax ratio, while decreasing levels of apoptotic cells, activating Caspase‑3 and closing the mPTP. These effects were blocked by VDAC1 overexpression and the results of molecular docking simulation studies revealed a direct interaction between TSN and VDAC1. In conclusion, TSN pretreatment effectively attenuated H9c2 cardiomyocyte damage in an A/R injury model and VDAC1‑mediated ferroptosis and apoptosis served a vital role in the protective effects of TSN.
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Copy and paste a formatted citation
Spandidos Publications style
Hu T, Zou H, Le S, Wang Y, Qiao Y, Yuan Y, Liu J, Lai S and Huang H: Tanshinone IIA confers protection against myocardial ischemia/reperfusion injury by inhibiting ferroptosis and apoptosis via VDAC1. Int J Mol Med 52: 109, 2023.
APA
Hu, T., Zou, H., Le, S., Wang, Y., Qiao, Y., Yuan, Y. ... Huang, H. (2023). Tanshinone IIA confers protection against myocardial ischemia/reperfusion injury by inhibiting ferroptosis and apoptosis via VDAC1. International Journal of Molecular Medicine, 52, 109. https://doi.org/10.3892/ijmm.2023.5312
MLA
Hu, T., Zou, H., Le, S., Wang, Y., Qiao, Y., Yuan, Y., Liu, J., Lai, S., Huang, H."Tanshinone IIA confers protection against myocardial ischemia/reperfusion injury by inhibiting ferroptosis and apoptosis via VDAC1". International Journal of Molecular Medicine 52.5 (2023): 109.
Chicago
Hu, T., Zou, H., Le, S., Wang, Y., Qiao, Y., Yuan, Y., Liu, J., Lai, S., Huang, H."Tanshinone IIA confers protection against myocardial ischemia/reperfusion injury by inhibiting ferroptosis and apoptosis via VDAC1". International Journal of Molecular Medicine 52, no. 5 (2023): 109. https://doi.org/10.3892/ijmm.2023.5312
Copy and paste a formatted citation
x
Spandidos Publications style
Hu T, Zou H, Le S, Wang Y, Qiao Y, Yuan Y, Liu J, Lai S and Huang H: Tanshinone IIA confers protection against myocardial ischemia/reperfusion injury by inhibiting ferroptosis and apoptosis via VDAC1. Int J Mol Med 52: 109, 2023.
APA
Hu, T., Zou, H., Le, S., Wang, Y., Qiao, Y., Yuan, Y. ... Huang, H. (2023). Tanshinone IIA confers protection against myocardial ischemia/reperfusion injury by inhibiting ferroptosis and apoptosis via VDAC1. International Journal of Molecular Medicine, 52, 109. https://doi.org/10.3892/ijmm.2023.5312
MLA
Hu, T., Zou, H., Le, S., Wang, Y., Qiao, Y., Yuan, Y., Liu, J., Lai, S., Huang, H."Tanshinone IIA confers protection against myocardial ischemia/reperfusion injury by inhibiting ferroptosis and apoptosis via VDAC1". International Journal of Molecular Medicine 52.5 (2023): 109.
Chicago
Hu, T., Zou, H., Le, S., Wang, Y., Qiao, Y., Yuan, Y., Liu, J., Lai, S., Huang, H."Tanshinone IIA confers protection against myocardial ischemia/reperfusion injury by inhibiting ferroptosis and apoptosis via VDAC1". International Journal of Molecular Medicine 52, no. 5 (2023): 109. https://doi.org/10.3892/ijmm.2023.5312
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