HIF‑1α protein SUMOylation is an important protective mechanism of action of hypothermia in hypoxic cardiomyocytes

  • Authors:
    • Huaqin Liu
    • Xiyun Bian
    • Meili Xu
    • Xiaofang Ma
    • Chunyan Zhang
    • Jinjin Jiang
    • Jianfeng Fu
    • Xiaozhi Liu
  • View Affiliations

  • Published online on: April 22, 2021     https://doi.org/10.3892/mmr.2021.12115
  • Article Number: 476
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Abstract

Different degrees of myocardial ischemia‑reperfusion injury during open‑heart surgery are inevitable. Therapeutic hypothermia is an important technique for reducing ischemia‑reperfusion injury; however, there are numerous potential adverse effects. Furthermore, the underlying molecular mechanisms of action of therapeutic hypothermia remain unclear. In the present study, rat hearts were perfused for 30 min and subjected to 30 min of regional ischemia, followed by 120 min of reperfusion. Animals received intraperitoneal injection of spectomycin B1 at 30 min prior to the start of surgery. Total myocardial area, infarct area, myocardial injury, and apoptosis were assessed. H9C2 cells were incubated for 24  h at 34˚C with 5% CO2 to simulate therapeutic hypothermic stress, and cell viability and mitochondrial injury were evaluated. The levels of protein SUMOylation, hypoxia‑inducible factor (HIF)‑1α and vascular endothelial growth factor (VEGF) were determined by western blot analysis. It was demonstrated that hypoxia significantly increased the overall modification by the small ubiquitin‑related modifier protein (SUMO) of various proteins in cardiomyocytes, both in vitro and ex vivo. In turn, this increased the protein levels of HIF‑1α, continuously stimulated downstream VEGF expression. Therapeutic hypothermia further increased protein SUMOylation, whereas inhibiting the SUMOylation pathway reduced the protective effect of therapeutic hypothermia on hypoxic cardiomyocytes. Overall, these data suggested that increasing SUMOylation of HIF‑1α may be an important molecular mechanism underlying the protective effects of therapeutic hypothermia following hypoxia in myocardial cells. These findings may aid in the use of therapeutic hypothermia for treatment of myocardial ischemia‑reperfusion and help avoid excessive side effects.
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June-2021
Volume 23 Issue 6

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
Liu H, Bian X, Xu M, Ma X, Zhang C, Jiang J, Fu J and Liu X: HIF‑1α protein SUMOylation is an important protective mechanism of action of hypothermia in hypoxic cardiomyocytes. Mol Med Rep 23: 476, 2021
APA
Liu, H., Bian, X., Xu, M., Ma, X., Zhang, C., Jiang, J. ... Liu, X. (2021). HIF‑1α protein SUMOylation is an important protective mechanism of action of hypothermia in hypoxic cardiomyocytes. Molecular Medicine Reports, 23, 476. https://doi.org/10.3892/mmr.2021.12115
MLA
Liu, H., Bian, X., Xu, M., Ma, X., Zhang, C., Jiang, J., Fu, J., Liu, X."HIF‑1α protein SUMOylation is an important protective mechanism of action of hypothermia in hypoxic cardiomyocytes". Molecular Medicine Reports 23.6 (2021): 476.
Chicago
Liu, H., Bian, X., Xu, M., Ma, X., Zhang, C., Jiang, J., Fu, J., Liu, X."HIF‑1α protein SUMOylation is an important protective mechanism of action of hypothermia in hypoxic cardiomyocytes". Molecular Medicine Reports 23, no. 6 (2021): 476. https://doi.org/10.3892/mmr.2021.12115