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A novel danshensu/tetramethypyrazine derivative attenuates oxidative stress‑induced autophagy injury via the AMPK‑mTOR‑Ulk1 signaling pathway in cardiomyocytes

  • Authors:
    • Caipeng Xie
    • Jingxiong Luo
    • Huihui Hu
    • Liang Wang
    • Pei Yu
    • Lipeng Xu
    • Yewei Sun
    • Yuqiang Wang
    • Luchen Shan
  • View Affiliations

  • Published online on: December 3, 2020     https://doi.org/10.3892/etm.2020.9550
  • Article Number: 118
  • Copyright: © Xie et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Myocardial ischemia/reperfusion injury (MIRI) is an inevitable and unsolved clinical problem in the treatment of ischemic heart diseases. Compound DT‑010 is a novel danshensu/tetramethylpyrazine derivative and was examined as a candidate for treating MIRI. In the present study, MTT, lactate dehydrogenase assay and Hoechst staining data indicated that DT‑010 attenuated tert‑butylhydroperoxide (t‑BHP)‑induced oxidative damage by increasing cell survival, reducing cell damage and decreasing apoptosis in H9c2 cardiomyocytes. Autophagy was assessed by western blotting for microtubule‑associated protein 1A/1B‑light chain 3 (LC3‑II and LC3‑I) expression, acridine orange and monodansylcadaverine staining for autophagosome formation and the monomeric red fluorescent protein‑green fluorescent protein‑LC3 assay for autophagic flow. t‑BHP‑induced cell damage was aggravated by the autophagy agonist rapamycin and alleviated by the autophagy blocker hydroxy‑chloroquine, suggesting that autophagy was involved in t‑BHP‑induced cardiomyocyte injury. DT‑010 pretreatment significantly prevented t‑BHP‑induced cell damage, which was partially but significantly abolished by rapamycin and significantly improved by hydroxy‑chloroquine treatment. DT‑010 treatment inhibited t‑BHP‑induced autophagy in H9c2 cells, reduced phosphorylation of 5'‑AMP‑activated protein kinase (AMPK) and promoted the phosphorylation of mTOR and unc‑51 like autophagy activating kinase 1 (Ulk1). To conclude, DT‑010 can serve as a potential candidate for myocardial ischemia‑reperfusion injury therapy. The cardioprotective effects of DT‑010 could be partially attributed to its inhibition of autophagy via the AMPK‑mTOR‑Ulk1 signaling pathway.
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February-2021
Volume 21 Issue 2

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Copy and paste a formatted citation
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Spandidos Publications style
Xie C, Luo J, Hu H, Wang L, Yu P, Xu L, Sun Y, Wang Y and Shan L: A novel danshensu/tetramethypyrazine derivative attenuates oxidative stress‑induced autophagy injury via the AMPK‑mTOR‑Ulk1 signaling pathway in cardiomyocytes. Exp Ther Med 21: 118, 2021.
APA
Xie, C., Luo, J., Hu, H., Wang, L., Yu, P., Xu, L. ... Shan, L. (2021). A novel danshensu/tetramethypyrazine derivative attenuates oxidative stress‑induced autophagy injury via the AMPK‑mTOR‑Ulk1 signaling pathway in cardiomyocytes. Experimental and Therapeutic Medicine, 21, 118. https://doi.org/10.3892/etm.2020.9550
MLA
Xie, C., Luo, J., Hu, H., Wang, L., Yu, P., Xu, L., Sun, Y., Wang, Y., Shan, L."A novel danshensu/tetramethypyrazine derivative attenuates oxidative stress‑induced autophagy injury via the AMPK‑mTOR‑Ulk1 signaling pathway in cardiomyocytes". Experimental and Therapeutic Medicine 21.2 (2021): 118.
Chicago
Xie, C., Luo, J., Hu, H., Wang, L., Yu, P., Xu, L., Sun, Y., Wang, Y., Shan, L."A novel danshensu/tetramethypyrazine derivative attenuates oxidative stress‑induced autophagy injury via the AMPK‑mTOR‑Ulk1 signaling pathway in cardiomyocytes". Experimental and Therapeutic Medicine 21, no. 2 (2021): 118. https://doi.org/10.3892/etm.2020.9550