Sunitinib mediates mitochondrial ROS production in adult rat cardiac fibroblasts via CaMKII oxidation

McMullen, CJ and Chalmers, S and Cunningham, MR and Currie, S (2020) Sunitinib mediates mitochondrial ROS production in adult rat cardiac fibroblasts via CaMKII oxidation. Heart, 106 (Suppl ). OP8. ISSN 1468-201X

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    Abstract

    Ca2+/calmodulin dependent protein kinase II (CaMKII) is a central mediator of Ca2+-induced signalling in the heart and regulates both normal cardiac physiology and pathology. Sunitinib malate is an oral Type I tyrosine kinase inhibitor (TKI) known to inhibit more than 50 kinases, with anti-angiogenic and anti-proliferative effects affiliated with off-target cardiotoxicity. Previous work has shown that chronic sunitinib treatment significantly increases CaMKII expression and activity and this correlates with significant cardiac dysfunction in vivo.1 Mitochondrial dysfunction, mediated by increased mitochondrial Ca2+ and resultant mitochondrial ROS production, has been proposed as an underlying mechanism for TKI-induced cardiotoxicity in cardiomyocytes.2 However, little is known of how TKIs may affect the non-contractile cells of the heart. Here, we have investigated whether sunitinib treatment increases mitochondrial ROS production in cardiac fibroblasts (CF) and whether CaMKII may play a role in this potential cardiotoxic mechanism

    Creators(s): McMullen, CJ, Chalmers, S ORCID logoORCID: https://orcid.org/0000-0002-8073-7576, Cunningham, MR ORCID logoORCID: https://orcid.org/0000-0001-6454-8671 and Currie, S ORCID logoORCID: https://orcid.org/0000-0002-4237-4428;
    Item type:Article
    ID code:72649
    Keywords:cardiac physiology, sunitinib, cardiac fibroblast, Pharmacy and materia medica, Pharmacology, Toxicology and Pharmaceutics(all)
    Subjects:Medicine > Pharmacy and materia medica
    Department:Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences
    Depositing user: Pure Administrator
    Date deposited:09 Jun 2020 15:31
    Last modified:21 Jan 2021 12:01
    Related URLs:
    URI:https://strathprints.strath.ac.uk/id/eprint/72649
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