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Article

TNF-α induces Drp1-mediated mitochondrial fragmentation during inflammatory cardiomyocyte injury

  • Authors:
    • Yue‑Liang Shen
    • Ying‑Zhou Shi
    • Gai‑Ge Chen
    • Lin‑Lin Wang
    • Ming‑Zhi Zheng
    • Hong‑Feng Jin
    • Ying‑Ying Chen
  • View Affiliations / Copyright

    Affiliations: Department of Pathology and Pathophysiology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, P.R. China, Center for Stem Cell and Tissue Engineering, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, P.R. China, Department of Pharmacology, Hangzhou Medical College, Hangzhou, Zhejiang 310053, P.R. China, Department of Cardiology, Zhejiang Hospital, Hangzhou, Zhejiang 310013, P.R. China
  • Pages: 2317-2327
    |
    Published online on: January 15, 2018
       https://doi.org/10.3892/ijmm.2018.3385
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Abstract

Dynamin-related peptide 1 (Drpl)-mediated mitochondrial fission is an important process associated with cardiac dysfunction under different pathological conditions. The aim of the present study was to investigate the expression of Drpl during inflammatory myocardial injury. Sprague‑Dawley rats were treated intraperitoneally with lipopolysaccharides (LPS). Furthermore, cultured H9C2 cardiomyocytes were treated with LPS, interleukin‑6 (IL‑6) and tumor necrosis factor‑α (TNF‑α). Total and mitochondrial proteins were isolated from the heart tissue of rats and from the H9C2 cardiomyocytes. Expression levels of Drp1 and RhoA were analyzed by western blotting. Mitochondrial morphology was determined using confocal laser microscopy. The levels of mitochondrial Drp1 and phosphorylated‑Drp1 (p‑Drp1) Ser616 were revealed to be increased in rats 6 h after injection with LPS (5, 10 or 20 mg/kg). Furthermore, treatment with LPS and IL‑6 did not demonstrate a significant effect on the expression of total and mitochondrial Drp1 in H9C2 cardiomyocytes in vitro; however, treatment with TNF‑α (20 ng/ml) significantly enhanced the levels of mitochondrial Drp1 and p‑Drp1 Ser616. Following TNF‑α treatment, the expression of Ras homolog gene family member A (RhoA) was also revealed to increase. Treatment with both Y‑27632 and fasudil, [Rho kinase (ROCK) inhibitors], was demonstrated to attenuate the otherwise TNF‑α‑induced increase in p‑Drp1 Ser616 and mitochondrial Drp1. In addition, it was revealed that Y‑27632 and fasudil may also attenuate the TNF‑α‑induced increase in mitochondrial fragmentation and cell viability. Therefore, the findings of the present study suggest that TNF‑α is the predominant inducer of Drp1 S616 phosphorylation during sepsis. The results of the present study also suggest that the RhoA/ROCK pathway may be involved in the phosphorylation and mitochondrial translocation of Drp1, which leads to mitochondrial fragmentation.
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Copy and paste a formatted citation
Spandidos Publications style
Shen YL, Shi YZ, Chen GG, Wang LL, Zheng MZ, Jin HF and Chen YY: TNF-α induces Drp1-mediated mitochondrial fragmentation during inflammatory cardiomyocyte injury. Int J Mol Med 41: 2317-2327, 2018.
APA
Shen, Y., Shi, Y., Chen, G., Wang, L., Zheng, M., Jin, H., & Chen, Y. (2018). TNF-α induces Drp1-mediated mitochondrial fragmentation during inflammatory cardiomyocyte injury. International Journal of Molecular Medicine, 41, 2317-2327. https://doi.org/10.3892/ijmm.2018.3385
MLA
Shen, Y., Shi, Y., Chen, G., Wang, L., Zheng, M., Jin, H., Chen, Y."TNF-α induces Drp1-mediated mitochondrial fragmentation during inflammatory cardiomyocyte injury". International Journal of Molecular Medicine 41.4 (2018): 2317-2327.
Chicago
Shen, Y., Shi, Y., Chen, G., Wang, L., Zheng, M., Jin, H., Chen, Y."TNF-α induces Drp1-mediated mitochondrial fragmentation during inflammatory cardiomyocyte injury". International Journal of Molecular Medicine 41, no. 4 (2018): 2317-2327. https://doi.org/10.3892/ijmm.2018.3385
Copy and paste a formatted citation
x
Spandidos Publications style
Shen YL, Shi YZ, Chen GG, Wang LL, Zheng MZ, Jin HF and Chen YY: TNF-α induces Drp1-mediated mitochondrial fragmentation during inflammatory cardiomyocyte injury. Int J Mol Med 41: 2317-2327, 2018.
APA
Shen, Y., Shi, Y., Chen, G., Wang, L., Zheng, M., Jin, H., & Chen, Y. (2018). TNF-α induces Drp1-mediated mitochondrial fragmentation during inflammatory cardiomyocyte injury. International Journal of Molecular Medicine, 41, 2317-2327. https://doi.org/10.3892/ijmm.2018.3385
MLA
Shen, Y., Shi, Y., Chen, G., Wang, L., Zheng, M., Jin, H., Chen, Y."TNF-α induces Drp1-mediated mitochondrial fragmentation during inflammatory cardiomyocyte injury". International Journal of Molecular Medicine 41.4 (2018): 2317-2327.
Chicago
Shen, Y., Shi, Y., Chen, G., Wang, L., Zheng, M., Jin, H., Chen, Y."TNF-α induces Drp1-mediated mitochondrial fragmentation during inflammatory cardiomyocyte injury". International Journal of Molecular Medicine 41, no. 4 (2018): 2317-2327. https://doi.org/10.3892/ijmm.2018.3385
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