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Tiron ameliorates high glucose‐induced cardiac myocyte apoptosis by PKC δ‐dependent inhibition of osteopontin
Author(s) -
Jiang Ping,
Zhang Deling,
Qiu Hong,
Yi Xianqi,
Zhang Yemin,
Cao Yingkang,
Zhao Bo,
Xia Zhongyuan,
Wang Changhua
Publication year - 2017
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/1440-1681.12762
Subject(s) - osteopontin , tiron , cardiac myocyte , protein kinase c , apoptosis , chemistry , myocyte , microbiology and biotechnology , medicine , pharmacology , signal transduction , biology , biochemistry , enzyme , superoxide
Summary 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 ( NRVM s), 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 NRVM s and the left ventricular cardiomyocytes from STZ ‐diabetic rat, accompanied with a reduction of osteopontin ( OPN ) levels as well as an inhibition of PKC δ phosphorylation. OPN knockdown protected NRVM s against HG ‐induced cell apoptosis. In addition, genetic inhibition of PKC δ mitigated HG ‐stimulated enhancement of intracellular OPN levels in NRVM s. These findings indicate that ROS ‐mediated activation of PKC δ upregulated OPN expression, leading to cardiac myocyte apoptosis. Interfering with ROS / PKC δ pathway by antioxidants such as tiron provides an optional therapeutic strategy for treatment and prevention of apoptosis‐related cardiovascular diseases including diabetic cardiomyopathy.