Xinnaotongluo liquid protects H9c2 cells from H/R-induced damage by regulating MDM2/STEAP3

PLoS One. 2024 Apr 19;19(4):e0302407. doi: 10.1371/journal.pone.0302407. eCollection 2024.

Abstract

Xinnaotongluo liquid has been used to improve the clinical symptoms of patients with myocardial infarction. However, the molecular mechanism of Xinnaotongluo liquid is not completely understood. H9c2 cells exposed to hypoxia/reoxygenation (H/R) was used to simulate damage to cardiomyocytes in myocardial infarction in vitro. The biological indicators of H9c2 cells were measured by cell counting kit-8, enzyme linked immunoabsorbent assay, and western blot assay. In H/R-induced H9c2 cells, a markedly reduced murine double minute 2 (MDM2) was observed. However, the addition of Xinnaotongluo liquid increased MDM2 expression in H/R-induced H9c2 cells. And MDM2 overexpression strengthened the beneficial effects of Xinnaotongluo liquid on H9c2 cells from the perspective of alleviating oxidative damage, cellular inflammation, apoptosis and ferroptosis of H/R-induced H9c2 cells. Moreover, MDM2 overexpression reduced the protein expression of p53 and Six-Transmembrane Epithelial Antigen of Prostate 3 (STEAP3). Whereas, STEAP3 overexpression hindered the function of MDM2-overexpression in H/R-induced H9c2 cells. Our results insinuated that Xinnaotongluo liquid could protect H9c2 cells from H/R-induced damage by regulating MDM2/STEAP3, which provide a potential theoretical basis for further explaining the working mechanism of Xinnaotongluo liquid.

MeSH terms

  • Animals
  • Apoptosis
  • Cell Hypoxia
  • Humans
  • Hypoxia* / metabolism
  • Male
  • Mice
  • Myocardial Infarction* / metabolism
  • Myocytes, Cardiac / metabolism
  • Proto-Oncogene Proteins c-mdm2 / genetics
  • Proto-Oncogene Proteins c-mdm2 / metabolism

Substances

  • MDM2 protein, human
  • Proto-Oncogene Proteins c-mdm2

Grants and funding

This study was supported by Heilongjiang Natural Science Foundation Project, LH2022H074. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.