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Previous studies have shown that cardiac myocyte apoptosis can be effectively inhibited by tiron administration in streptozotocin (<jats:styled-content style=\"fixed-case\">STZ<\/jats:styled-content>)\u2010induced diabetic rats, primary neonatal rat cardiomyocytes (<jats:styled-content style=\"fixed-case\">NRVM<\/jats:styled-content>s), and H9c2 embryonic rat cardiomyocytes. However, the underlying signalling mechanism is ill\u2010defined. In the present study, we found that tiron supplementation significantly inhibited apoptosis of high glucose (<jats:styled-content style=\"fixed-case\">HG<\/jats:styled-content>)\u2010treated <jats:styled-content style=\"fixed-case\">NRVM<\/jats:styled-content>s and the left ventricular cardiomyocytes from <jats:styled-content style=\"fixed-case\">STZ<\/jats:styled-content>\u2010diabetic rat, accompanied with a reduction of osteopontin (<jats:styled-content style=\"fixed-case\">OPN<\/jats:styled-content>) levels as well as an inhibition of <jats:styled-content style=\"fixed-case\">PKC<\/jats:styled-content>\u03b4 phosphorylation. <jats:styled-content style=\"fixed-case\">OPN<\/jats:styled-content> knockdown protected <jats:styled-content style=\"fixed-case\">NRVM<\/jats:styled-content>s against <jats:styled-content style=\"fixed-case\">HG<\/jats:styled-content>\u2010induced cell apoptosis. In addition, genetic inhibition of <jats:styled-content style=\"fixed-case\">PKC<\/jats:styled-content>\u03b4 mitigated <jats:styled-content style=\"fixed-case\">HG<\/jats:styled-content>\u2010stimulated enhancement of intracellular <jats:styled-content style=\"fixed-case\">OPN<\/jats:styled-content> levels in <jats:styled-content style=\"fixed-case\">NRVM<\/jats:styled-content>s. These findings indicate that <jats:styled-content style=\"fixed-case\">ROS<\/jats:styled-content>\u2010mediated activation of <jats:styled-content style=\"fixed-case\">PKC<\/jats:styled-content>\u03b4 upregulated <jats:styled-content style=\"fixed-case\">OPN<\/jats:styled-content> expression, leading to cardiac myocyte apoptosis. Interfering with <jats:styled-content style=\"fixed-case\">ROS<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">PKC<\/jats:styled-content>\u03b4 pathway by antioxidants such as tiron provides an optional therapeutic strategy for treatment and prevention of apoptosis\u2010related cardiovascular diseases including diabetic cardiomyopathy.<\/jats:p>","DOI":"10.1111\/1440-1681.12762","type":"journal-article","created":{"date-parts":[[2017,4,10]],"date-time":"2017-04-10T14:20:02Z","timestamp":1491834002000},"page":"760-770","source":"Crossref","is-referenced-by-count":16,"title":["Tiron ameliorates high glucose\u2010induced cardiac myocyte apoptosis by <scp>PKC<\/scp>\u03b4\u2010dependent inhibition of osteopontin"],"prefix":"10.1111","volume":"44","author":[{"given":"Ping","family":"Jiang","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Medicine The People's Hospital of Gongan County  Gongan China"},{"name":"Department of Pathology &amp; 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