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Differential changes in cardiac myofibrillar and sarcoplasmic reticular gene expression in alloxan-induced diabetes

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Abstract

In order to examine the relationship between heart dysfunction and subcellular abnormalities as well as molecular mechanisms during the development of diabetes, we studied changes in cardiac performance, myofibrillar as well as sarcoplasmic reticular (SR) activities, and cardiac gene expression at different time intervals upon inducing diabetes in rats by an injection of alloxan (65 mg/kg; i.v.). Cardiac dysfunction was associated with a depression in myofibrillar Ca2+-stimulated ATPase and changes in myosin isozyme composition at 2-12 weeks of inducing diabetes. A reduction in SR Ca2+-uptake and Ca2+-pump (SERCA2) activities was evident at 10 days to 12 weeks of inducing diabetes. Alterations in cardiac function during 2-12 weeks of diabetes show a linear relationship with changes in myofibrils and SR membranes. Furthermore, alterations in cardiac function as well as myofibrillar and SR activities in 4 week diabetic animals were normalized upon treatment with insulin for 4 weeks. The steady-state mRNA abundance for α-myosin heavy chain in the heart was decreased at 2 and 3 weeks but was unchanged at 5 and 6 weeks, whereas mRNA levels for β-myosin heavy chain remained elevated during 2-6 weeks after inducing diabetes. SERCA2 mRNA abundance in diabetic heart was significantly increased at 3 and 5 weeks but was unaltered at 2 and 6 weeks. These results support the view that heart dysfunction in diabetes may be a consequence of myofibrillar and SR abnormalities; however, defects in myofibrillar proteins, unlike those in the SR membranes, appear to be due to changes in their gene expression.

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Authors and Affiliations

  1. Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre and Department of Physiology, Faculty of Medicine, University of Manitoba, Winnipeg, Canada

    Leonard Golfman, Ian M.C. Dixon, Donald Chapman & Naranjan S. Dhalla

  2. Department of Internal Medicine, Aoto Hospital, Jikei University, Tokyo, Japan

    Nobuakira Takeda

Authors
  1. Leonard Golfman
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  2. Ian M.C. Dixon
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  3. Nobuakira Takeda
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  4. Donald Chapman
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  5. Naranjan S. Dhalla
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Golfman, L., Dixon, I.M., Takeda, N. et al. Differential changes in cardiac myofibrillar and sarcoplasmic reticular gene expression in alloxan-induced diabetes. Mol Cell Biochem 200, 15–25 (1999). https://doi.org/10.1023/A:1006950218597

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