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- Title
Depressed levels of Ca2+-cycling proteins may underlie sarcoplasmic reticulum dysfunction in the diabetic heart.
- Authors
Netticadan, Thomas; Temsah, Rana M.; Kent, Ardeep; Elimban, Vijayan; Dhalla, Naranjan S.; Netticadan, T; Temsah, R M; Kent, A; Elimban, V; Dhalla, N S
- Abstract
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.
- Subjects
CALCIUM-binding proteins; DIABETES; CALCIUM metabolism; HEART metabolism; CYTOPLASM; ANIMAL experimentation; CARRIER proteins; COMPARATIVE studies; HEART; RESEARCH methodology; MEDICAL cooperation; PHOSPHATASES; PHOSPHORYLATION; RATS; RESEARCH; TRANSFERASES; EVALUATION research; PHYSIOLOGY
- Publication
Diabetes, 2001, Vol 50, Issue 9, p2133
- ISSN
0012-1797
- Publication type
journal article
- DOI
10.2337/diabetes.50.9.2133