Genistein Protects H9c2 Cardiomyocytes against Chemical Hypoxia-Induced Injury via Inhibition of Apoptosis

Pharmacology. 2019;103(5-6):282-290. doi: 10.1159/000497061. Epub 2019 Feb 26.

Abstract

Background/aims: Hypoxia can induce cell injury in cardiomyocytes and further lead to cardiovascular diseases. Genistein (Gen), the predominant isoflavone found in soy products, has shown protective effects on cardiovascular system. The aim of the present study was to investigate the cardioprotective effect of Gen against chemical hypoxia-induced injury.

Methods: Cobalt chloride (CoCl2) was administrated to trigger chemical hypoxia in H9c2 cardiomyocytes. Cell proliferation was detected by using MTT assay. The expression level of hypoxia-related proteins (hypoxia-inducible factor [HIF]-1α and Notch-1) and apoptosis-related proteins (B cell lymphoma [Bcl]-2, Bax, and caspase-3) were evaluated by Western blot analysis.

Results: In response to hypoxia, cell viability was reduced dramatically, whereas the expression of HIF-1α was upregulated. Hypoxia also induced cardiomyocytes apoptosis by reducing the ratio of Bcl-2/Bax and increasing expression of caspase-3. Interestingly, Gen attenuated CoCl2-induced cell death and suppressed HIF-1α expression, as well as upregulated the expression of Notch-1. Furthermore, Gen could antagonize CoCl2-induced apoptosis through upregulating Bcl-2/Bax ratio and inhibiting caspase-3 expression.

Conclusions: Gen prevents chemical hypoxia-induced cell apoptosis through inhibition of the mitochondrial apoptotic pathway, exerting protective effects on H9c2 cardiomyocytes.

Keywords: Apoptosis; Cardiomyocytes; Genistein; Hypoxia.

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Blotting, Western
  • Cardiotonic Agents / pharmacology
  • Cell Hypoxia / drug effects*
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Cobalt / toxicity
  • Genistein / pharmacology*
  • Mitochondria / drug effects
  • Mitochondria / pathology
  • Myocytes, Cardiac / drug effects*
  • Myocytes, Cardiac / pathology
  • Rats
  • Up-Regulation / drug effects

Substances

  • Cardiotonic Agents
  • Cobalt
  • Genistein
  • cobaltous chloride