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Article Open Access

Tetramethylpyrazine protects retinal ganglion cells against H2O2‑induced damage via the microRNA‑182/mitochondrial pathway

  • Authors:
    • Xinmin Li
    • Qiuli Wang
    • Yanfan Ren
    • Xiaomin Wang
    • Huaxu Cheng
    • Hua Yang
    • Baojun Wang
  • View Affiliations / Copyright

    Affiliations: Department of Ophthalmology, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan 453100, P.R. China, Department of Ophthalmology, The Third Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan 453000, P.R. China
    Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 503-512
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    Published online on: May 29, 2019
       https://doi.org/10.3892/ijmm.2019.4214
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Abstract

Glaucoma is the leading cause of irreversible blindness worldwide; the apoptosis of the retinal ganglion cells (RGCs) is a hallmark of glaucoma. Tetramethylpyrazine (TMP) is the main active component of Ligusticum wallichii Franchat, and has been demonstrated to improve a variety of injuries through its antioxidative and antiapoptotic properties. However, these effects of TMP on glaucoma have not been studied. The present study aimed to investigate the potential role of TMP in glaucoma and to elucidate its possible mechanisms responsible for these effects. An in vitro model was generated, in which primary RGCs (PRGCs) were treated with H2O2. Our study revealed that TMP protected against H2O2‑induced injury to PRGCs, as evidenced by enhanced cell viability, reduced caspase 3 activity and decreased cell apoptosis. We also reported that TMP treatment inhibited reactive oxygen species (ROS) production and malondialdehyde levels, but upregulated the antioxidative enzyme superoxide dismutase. In particular, TMP significantly increased the expression of microRNA‑182‑5p (miR‑182) in H2O2‑treated PRGCs, which was selected as the target miRNA for further research. In addition, our findings suggested that the protective effects of TMP on H2O2‑induced injury were attenuated by knockdown of miR‑182. The results of a luciferase reporter assay demonstrated that Bcl‑2 interacting protein 3 (BNIP3), an effector of mitochondria‑mediated apoptosis, was a direct target of miR‑182. In addition, TMP treatment significantly decreased the expression of BNIP3, Bax, cleaved‑caspase‑3 and cleaved‑poly(ADP‑ribose)polymerase, but increased that of Bcl‑2. Also, TMP treatment decreased the release of cytochrome c from mitochondria and improved mitochondrial membrane potential in H2O2‑treated RGCs. Of note, the inhibitory effects of TMP on the mitochondrial apoptotic pathway were suggested to be reversed by knockdown of miR‑182. Collectively, our findings provide novel evidence that TMP protects PRGCs against H2O2‑induced damage through suppressing apoptosis and oxidative stress via the miR‑182/mitochondrial apoptotic pathway.
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Copy and paste a formatted citation
Spandidos Publications style
Li X, Wang Q, Ren Y, Wang X, Cheng H, Yang H and Wang B: Tetramethylpyrazine protects retinal ganglion cells against H2O2‑induced damage via the microRNA‑182/mitochondrial pathway. Int J Mol Med 44: 503-512, 2019.
APA
Li, X., Wang, Q., Ren, Y., Wang, X., Cheng, H., Yang, H., & Wang, B. (2019). Tetramethylpyrazine protects retinal ganglion cells against H2O2‑induced damage via the microRNA‑182/mitochondrial pathway. International Journal of Molecular Medicine, 44, 503-512. https://doi.org/10.3892/ijmm.2019.4214
MLA
Li, X., Wang, Q., Ren, Y., Wang, X., Cheng, H., Yang, H., Wang, B."Tetramethylpyrazine protects retinal ganglion cells against H2O2‑induced damage via the microRNA‑182/mitochondrial pathway". International Journal of Molecular Medicine 44.2 (2019): 503-512.
Chicago
Li, X., Wang, Q., Ren, Y., Wang, X., Cheng, H., Yang, H., Wang, B."Tetramethylpyrazine protects retinal ganglion cells against H2O2‑induced damage via the microRNA‑182/mitochondrial pathway". International Journal of Molecular Medicine 44, no. 2 (2019): 503-512. https://doi.org/10.3892/ijmm.2019.4214
Copy and paste a formatted citation
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Spandidos Publications style
Li X, Wang Q, Ren Y, Wang X, Cheng H, Yang H and Wang B: Tetramethylpyrazine protects retinal ganglion cells against H2O2‑induced damage via the microRNA‑182/mitochondrial pathway. Int J Mol Med 44: 503-512, 2019.
APA
Li, X., Wang, Q., Ren, Y., Wang, X., Cheng, H., Yang, H., & Wang, B. (2019). Tetramethylpyrazine protects retinal ganglion cells against H2O2‑induced damage via the microRNA‑182/mitochondrial pathway. International Journal of Molecular Medicine, 44, 503-512. https://doi.org/10.3892/ijmm.2019.4214
MLA
Li, X., Wang, Q., Ren, Y., Wang, X., Cheng, H., Yang, H., Wang, B."Tetramethylpyrazine protects retinal ganglion cells against H2O2‑induced damage via the microRNA‑182/mitochondrial pathway". International Journal of Molecular Medicine 44.2 (2019): 503-512.
Chicago
Li, X., Wang, Q., Ren, Y., Wang, X., Cheng, H., Yang, H., Wang, B."Tetramethylpyrazine protects retinal ganglion cells against H2O2‑induced damage via the microRNA‑182/mitochondrial pathway". International Journal of Molecular Medicine 44, no. 2 (2019): 503-512. https://doi.org/10.3892/ijmm.2019.4214
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