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
| Autor: | Vijaya Padma Viswanadha, I-Chieh Huang, Wei Wen Kuo, Kuan Ho Lin, Chung-Hung Liu, Chih Yang Huang, Yu-Min Wei, Jian-Sheng Liu |
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| Rok vydání: | 2021 |
| Předmět: |
Small interfering RNA
medicine.medical_treatment Apoptosis Sulfides Insulin-like growth factor-binding protein chemistry.chemical_compound medicine Extracellular Humans Myocytes Cardiac chemistry.chemical_classification Reactive oxygen species biology Growth factor General Chemistry Hydrogen Peroxide Hypoxia-Inducible Factor 1 alpha Subunit Cell biology Allyl Compounds Diallyl trisulfide Glucose Insulin-Like Growth Factor Binding Protein 3 chemistry Hypoxia-inducible factors biology.protein General Agricultural and Biological Sciences Reactive Oxygen Species |
| Zdroj: | Journal of agricultural and food chemistry. 69(39) |
| ISSN: | 1520-5118 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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