Diallyl Trisulfide Suppresses High-Glucose-Induced Cardiomyocyte Apoptosis by Targeting Reactive Oxygen Species-Mediated Hypoxia-Inducible Factor-1α/Insulin-like Growth Factor Binding Protein 3 Activation.

Abstract

It has been reported that 80% of diabetic patients die due to cardiovascular diseases. We previously demonstrated that activated hypoxia-inducible factor-1α (HIF-1 α)/insulin-like growth factor binding protein-3 (IGFBP-3) signaling by reactive oxygen species (ROS)-regulated prolyl hydroxylase domain-containing protein (PHD) is involved in high-glucose (HG)-induced cardiac apoptosis. Diallyl trisulfide (DATS), a garlic component, shows the strongest inhibitory effect on diabetic cardiomyopathy. In this study, we investigated whether HIF-1α/IGFBP-3 signaling governs the antiapoptotic effect by DATS on HG-exposed cardiomyocytes. It was observed that significantly increased levels of cell apoptosis and decreased Akt phosphorylation were reversed by DATS in HG-exposed cardiac cells. H2O2 and PHD small interfering RNA treatments increased HIF-1α and IGFBP-3 protein levels, which were decreased by DATS treatment. Overexpression of HIF-1α and IGFBP-3 increased HG-induced cell apoptosis, which was suppressed by DATS. The coimmunoprecipitation assay results showed that DATS not only increased the IGF-1 level and reduced IGFBP-3 level but also suppressed their extracellular association for cardiac cells exposed to HG. Experiments using neonatal cardiomyocytes and hearts showed similar results. These findings indicate that the effect of ROS-regulated PHD on the activation of HIF-1α/IGFBP-3 signaling governs the antiapoptotic effect by DATS on HG-exposed cardiomyocytes.

• Authors: Kuan-Ho Lin, Yu-Min Wei, Chung-Hung Liu, Jian-Sheng Liu, I-Chieh Huang, Vijaya Padma Viswanadha, Chih-Yang Huang, Wei-Wen Kuo
• Journal: Journal of agricultural and food chemistry (J Agric Food Chem) Vol. 69 Issue 39 Pg. 11696-11708 (Oct 06 2021) ISSN: 1520-5118 [Electronic] United States
• PMID: 34558885 (Publication Type: Journal Article)

Chemical References

• Allyl Compounds
• Hypoxia-Inducible Factor 1, alpha Subunit
• Insulin-Like Growth Factor Binding Protein 3
• Reactive Oxygen Species
• Sulfides
• diallyl trisulfide
• Hydrogen Peroxide
• Glucose

Topics

• Allyl Compounds
• Apoptosis
• Glucose
• Humans
• Hydrogen Peroxide
• Hypoxia-Inducible Factor 1, alpha Subunit (genetics)
• Insulin-Like Growth Factor Binding Protein 3 (genetics)
• Myocytes, Cardiac (metabolism)
• Reactive Oxygen Species (metabolism)
• Sulfides