Modification of Ca2+-handling in cardiomyocytes by redox sensitive mechanisms in response to ouabain
| Autor: | Harjot K. Saini-Chohan, Larry V. Hryshko, Naranjan S. Dhalla, Yan-Jun Xu |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Cardiotonic Agents
Physiology Mitogen-activated protein kinase kinase Biology Ouabain Rats Sprague-Dawley Wortmannin chemistry.chemical_compound Physiology (medical) Ca2+/calmodulin-dependent protein kinase medicine Animals Myocytes Cardiac Calphostin Enzyme Inhibitors Na+/K+-ATPase Cells Cultured Protein kinase C Pharmacology Free Radical Scavengers General Medicine Protein-Tyrosine Kinases Molecular biology Rats Spectrometry Fluorescence chemistry Calcium Mitogen-Activated Protein Kinases Sodium-Potassium-Exchanging ATPase Reactive Oxygen Species Oxidation-Reduction Tyrosine kinase medicine.drug |
| Zdroj: | Canadian Journal of Physiology and Pharmacology. 91:45-55 |
| ISSN: | 1205-7541 0008-4212 |
| DOI: | 10.1139/cjpp-2012-0215 |
| Popis: | We examined the role of redox-sensitive signal transduction mechanisms in modifying the changes in [Ca2+]iproduced by ouabain upon incubating adult rat cardiomyocytes with antioxidants or inhibitors of different protein kinases and monitoring alterations in fura-2 fluorescence. Ouabain increased basal [Ca2+]i, augmented the KCl-induced increase in [Ca2+]i, and promoted oxyradical production in cardiomyocytes. These actions of ouabain were attenuated by an oxyradical scavenging mixture (superoxide dismutase plus catalase), and the antioxidants (N-acetyl-l-cysteine and N-(2-mercaptoproprionyl)glycine). An inhibitor of MAP kinase (PD98059) depressed the ouabain-induced increase in [Ca2+], whereas inhibitors of tyrosine kinase (tyrphostin and genistein) and PI3 kinase (Wortmannin and LV294002) enhanced the ouabain-induced increase in [Ca2+]i. Inhibitors of protein kinase C (calphostin and bisindolylmalaimide) augmented the ouabain-induced increase in [Ca2+]i, whereas stimulation of protein kinase C by a phorbol ester (phorbol 12-myristate 13-acetate) depressed the action of ouabain. These results suggest that ouabain-induced inhibition of Na+–K+ATPase may alter the redox status of cardiomyocytes through the production of oxyradicals, and increase the activities of various protein kinases. Thus, these redox-sensitive signal transduction mechanisms involving different protein kinases may modify Ca2+-handling sites in cardiomyocytes and determine the magnitude of net increase in [Ca2+]iin response to ouabain. |
| Databáze: | OpenAIRE |
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