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Troponin subunits contribute to altered myosin ATPase activity in diabetic cardiomyopathy

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Abstract

Our group has documented that myocardial performance is impaired in the hearts of chronically diabetic rats and rabbits. Abnormalities in the contractile proteins and regulatory proteins may be responsible for the mechanical defects in the streptozotocin (STZ)-diabetic hearts. Previously, the major focus of our research on contractile proteins in abnormal states has concentrated on myosin ATPase and its isoenzymes. Our present study is based on the overall hypothesis that regulatory proteins, in addition to contractile protein, myosin contribute to altered cardiac contractile performance in the rat model of diabetic cardiomyopathy. The purpose of our research was to define the role of cardiac regulatory proteins (troponin-tropomyosin) in the regulation of actomyosin system in diabetic cardiomyopathy.

For baseline data, myofibrillar ATPase studies were conducted in the myofibrils from control and diabetic rats. To focus on the regulatory proteins (troponin and tropomyosin), individual proteins of the cardiac system were reconstituted under controlled conditions. By this approach, myosin plus actin and troponin-tropomyosin from the normal and diabetic animals could be studied enzymatically. The proteins were isolated from the cardiac muscle of control and STZ-diabetic (4 weeks) rats. Sodium dodecyl sulfate gel electrophoretic patterns demonstrate differences in the cardiac TnT and TnI regions of diabetic animals suggesting the different amounts of TnT and/or TnI or possibly different cardiac isozymes in the regulatory protein complex. Myofibrils probed with a monoclonal antibody TnI-1 (specific for adult cardiac TnI) show a downregulation of cardiac TnI in diabetics when compared to its controls. Enzymatic data confirm a diminished calcium sensitivity in the regulation of the cardiac actomyosin system when regulatory protein(s) complex was recombined from diabetic hearts. Actomyosin ATPase activity in the hearts of diabetic animals was partially reversed when myosin from diabetic rats was regulated with the regulatory protein complex isolated from control hearts. To our knowledge, this is the first study which demonstrates that the regulatory proteins from normal hearts can upregulate cardiac myosin isolated from a pathologic rat model of diabetes. This diminished calcium sensitivity along with shifts in cardiac myosin heavy chain (V1→V3) may be partially responsible for the impaired cardiac function in the hearts of chronic diabetic rats. (Mol Cell Biochem151: 165–172, 1995)

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Authors and Affiliations

  1. Division of Cardiology, Department of Medicine, Montefiore Medical Center, 111 East 210th Street, 10467, Bronx, NY, USA

    Ashwani Malhotra, M. Cecilia Lopez & Antonio Nakouzi

  2. Albert Einstein College of Medicine, Bronx, NY, USA

    Ashwani Malhotra, M. Cecilia Lopez & Antonio Nakouzi

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  1. Ashwani Malhotra
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  2. M. Cecilia Lopez
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  3. Antonio Nakouzi
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Malhotra, A., Lopez, M.C. & Nakouzi, A. Troponin subunits contribute to altered myosin ATPase activity in diabetic cardiomyopathy. Mol Cell Biochem 151, 165–172 (1995). https://doi.org/10.1007/BF01322339

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  • DOI: https://doi.org/10.1007/BF01322339

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