Depressed Levels of Ca2+-Cycling Proteins May Underlie Sarcoplasmic Reticulum Dysfunction in the Diabetic Heart
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- Thomas Netticadan
- Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, Winnipeg, Canada, and the Department of Physiology, Faculty of Medicine, University of Manitoba, Winnipeg, Canada
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- Rana M. Temsah
- Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, Winnipeg, Canada, and the Department of Physiology, Faculty of Medicine, University of Manitoba, Winnipeg, Canada
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- Ardeep Kent
- Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, Winnipeg, Canada, and the Department of Physiology, Faculty of Medicine, University of Manitoba, Winnipeg, Canada
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- Vijayan Elimban
- Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, Winnipeg, Canada, and the Department of Physiology, Faculty of Medicine, University of Manitoba, Winnipeg, Canada
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- Naranjan S. Dhalla
- Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, Winnipeg, Canada, and the Department of Physiology, Faculty of Medicine, University of Manitoba, Winnipeg, Canada
書誌事項
- 公開日
- 2001-09-01
- DOI
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- 10.2337/diabetes.50.9.2133
- 公開者
- American Diabetes Association
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説明
<jats:p>In view of the depressed sarcoplasmic reticulum (SR) Ca2+-pump and Ca2+-release activities in the diabetic heart and the critical role of phosphorylation in regulating the SR function, we examined the status of Ca2+-calmodulin–dependent protein kinase (CaMK) and cAMP-dependent protein kinase (PKA)-mediated phosphorylations in the diabetic heart. Diabetes was induced in male Sprague-Dawley rats by an injection of streptozotocin (65 mg/kg i.v.), and the animals were killed 6 weeks later for assessment of the ventricular SR function. Depressed cardiac performance and SR Ca2+-uptake and -release activities in diabetic animals were accompanied by a significant decrease in the level of SR Ca2+-cycling proteins, such as ryanodine receptor, Ca2+-pump ATPase, and phospholamban. On the other hand, the CaMK- and PKA-mediated phosphorylations of these Ca2+-cycling proteins, the endogenous SR CaMK and PKA activities, and the endogenous SR and cytosolic phosphatase activities were increased in the diabetic heart. Treatment of 3-week diabetic animals with insulin partially or fully prevented the diabetes-induced changes in cardiac performance, SR Ca2+-uptake and -release activites, and SR protein content, whereas the diabetes-induced changes in SR CaMK- and PKA-mediated phosphorylations and activities, as well as phosphatase activities, were not significantly affected. These results suggest that the reduced content of the Ca2+-cycling proteins, unlike alterations in PKA and phosphatase activities, appear to be the major defect underlying SR dysfunction in the diabetic heart.</jats:p>
収録刊行物
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- Diabetes
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Diabetes 50 (9), 2133-2138, 2001-09-01
American Diabetes Association