Defective phosphatidic acid–phospholipase C signaling in diabetic cardiomyopathy
| Autor: | J. Alejandro Austria, Nidhi Sahi, Grant N. Pierce, Thane G. Maddaford, Vincenzo Panagia, Paramjit S. Tappia, Cecilia Hurtado, Elena Dibrov |
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| Rok vydání: | 2004 |
| Předmět: |
Male
Inotrope medicine.medical_specialty medicine.medical_treatment Biophysics Phosphatidic Acids Inositol 1 4 5-Trisphosphate Biochemistry Diabetes Mellitus Experimental Rats Sprague-Dawley Basal (phylogenetics) chemistry.chemical_compound Internal medicine Diabetes mellitus Diabetic cardiomyopathy medicine Animals Myocytes Cardiac Molecular Biology Cells Cultured Phospholipase C Chemistry Insulin Cell Biology Phosphatidic acid medicine.disease Myocardial Contraction Rats Isoenzymes Kinetics Endocrinology Type C Phospholipases Calcium Signal transduction Cardiomyopathies Phospholipase C delta Diabetic Angiopathies Signal Transduction |
| Zdroj: | Biochemical and Biophysical Research Communications. 316:280-289 |
| ISSN: | 0006-291X |
| DOI: | 10.1016/j.bbrc.2004.02.045 |
| Popis: | The effects of exogenous phosphatidic acid (PA) on Ca2+ transients and contractile activity were studied in cardiomyocytes isolated from chronic streptozotocin-induced diabetic rats. In control cells, 25 μM PA induced a significant increase in active cell shortening and Ca2+ transients. PA increased IP3 generation in the control cardiomyocytes and its inotropic effects were blocked by a phospholipase C inhibitor. In cardiomyocytes from diabetic rats, PA induced a 25% decrease in active cell shortening and no significant effect on Ca2+ transients. Basal and PA-induced IP3 generation in diabetic rat cardiomyocytes was 3-fold lower as compared to control cells. Sarcolemmal membrane PLC activity was impaired. Insulin treatment of the diabetic animals resulted in a partial recovery of PA responses. Our results, therefore, identify an important defect in the PA-PLC signaling pathway in diabetic rat cardiomyocytes, which may have significant implications for heart dysfunction during diabetes. |
| Databáze: | OpenAIRE |
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