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- Title
Tiron ameliorates high glucose-induced cardiac myocyte apoptosis by PKCδ-dependent inhibition of osteopontin.
- Authors
Jiang, Ping; Zhang, Deling; Qiu, Hong; Yi, Xianqi; Zhang, Yemin; Cao, Yingkang; Zhao, Bo; Xia, Zhongyuan; Wang, Changhua
- 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.
- Subjects
OSTEOPONTIN; STREPTOZOTOCIN; HEART cells; APOPTOSIS; PROTEIN kinase C
- Publication
Clinical & Experimental Pharmacology & Physiology, 2017, Vol 44, Issue 7, p760
- ISSN
0305-1870
- Publication type
Article
- DOI
10.1111/1440-1681.12762