Tiron ameliorates high glucose-induced cardiac myocyte apoptosis by PKCδ-dependent inhibition of osteopontin
| Autor: | Ping Jiang, Hong Qiu, Bo Zhao, Yingkang Cao, Zhongyuan Xia, Yemin Zhang, Xianqi Yi, Deling Zhang, Changhua Wang |
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| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine medicine.medical_specialty Physiology Apoptosis 030204 cardiovascular system & hematology Pharmacology Cell Line Diabetes Mellitus Experimental Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Downregulation and upregulation Physiology (medical) Diabetic cardiomyopathy Internal medicine medicine Animals Myocytes Cardiac Osteopontin Phosphorylation Tiron Dose-Response Relationship Drug biology Cardiac myocyte medicine.disease Streptozotocin Rats Protein Kinase C-delta Glucose 030104 developmental biology Endocrinology chemistry 1 2-Dihydroxybenzene-3 5-Disulfonic Acid Disodium Salt biology.protein Intracellular medicine.drug |
| Zdroj: | Clinical and Experimental Pharmacology and Physiology. 44:760-770 |
| ISSN: | 0305-1870 |
| Popis: | Tiron functions as an effective antioxidant alleviating the intracellular reactive oxygen species (ROS) or the acute toxic metal overload. Previous studies have shown that cardiac myocyte apoptosis can be effectively inhibited by tiron administration in streptozotocin (STZ)-induced diabetic rats, primary neonatal rat cardiomyocytes (NRVMs), and H9c2 embryonic rat cardiomyocytes. However, the underlying signalling mechanism is ill-defined. In the present study, we found that tiron supplementation significantly inhibited apoptosis of high glucose (HG)-treated NRVMs and the left ventricular cardiomyocytes from STZ-diabetic rat, accompanied with a reduction of osteopontin (OPN) levels as well as an inhibition of PKCδ phosphorylation. OPN knockdown protected NRVMs against HG-induced cell apoptosis. In addition, genetic inhibition of PKCδ mitigated HG-stimulated enhancement of intracellular OPN levels in NRVMs. These findings indicate that ROS-mediated activation of PKCδ upregulated OPN expression, leading to cardiac myocyte apoptosis. Interfering with ROS/PKCδ pathway by antioxidants such as tiron provides an optional therapeutic strategy for treatment and prevention of apoptosis-related cardiovascular diseases including diabetic cardiomyopathy. |
| Databáze: | OpenAIRE |
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