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Tiron ameliorates high glucose-induced cardiac myocyte apoptosis by PKCδ-dependent inhibition of osteopontin.
- Source :
-
Clinical and experimental pharmacology & physiology [Clin Exp Pharmacol Physiol] 2017 Jul; Vol. 44 (7), pp. 760-770. - Publication Year :
- 2017
-
Abstract
- 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.<br /> (© 2017 John Wiley & Sons Australia, Ltd.)
- Subjects :
- Animals
Cell Line
Diabetes Mellitus, Experimental pathology
Dose-Response Relationship, Drug
Male
Mice
Myocytes, Cardiac pathology
Phosphorylation drug effects
Rats
1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt pharmacology
Apoptosis drug effects
Glucose pharmacology
Myocytes, Cardiac cytology
Myocytes, Cardiac drug effects
Osteopontin antagonists & inhibitors
Protein Kinase C-delta metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1440-1681
- Volume :
- 44
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Clinical and experimental pharmacology & physiology
- Publication Type :
- Academic Journal
- Accession number :
- 28394420
- Full Text :
- https://doi.org/10.1111/1440-1681.12762