Increased nitration of sarcoplasmic reticulum Ca2+-ATPase in human heart failure
| Autor: | Robert A. Haworth, Andrew J. Lokuta, Katherine T. Potter, Nathan A. Maertz, Héctor H. Valdivia, Sivan Vadakkadath Meethal, Timothy J. Kamp |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Adult
Male medicine.medical_specialty Adolescent ATPase Heart Ventricles Blotting Western chemistry.chemical_element Calcium-Transporting ATPases Calcium Nitric oxide Sarcoplasmic Reticulum Calcium-Transporting ATPases Contractility chemistry.chemical_compound Physiology (medical) Internal medicine medicine Myocyte Humans Myocytes Cardiac Phosphorylation Heart Failure biology business.industry Nitrotyrosine Endoplasmic reticulum Myocardium Middle Aged medicine.disease Isoenzymes Sarcoplasmic Reticulum Endocrinology chemistry Heart failure cardiovascular system biology.protein Tyrosine Female Cardiology and Cardiovascular Medicine business |
| Zdroj: | Circulation. 111(8) |
| ISSN: | 1524-4539 |
| Popis: | Background— Reduced sarcoplasmic reticulum (SR) Ca 2+ -ATPase (SERCA2a isoform) activity is a major determinant of reduced contractility in heart failure. Ca 2+ -ATPase inactivation can occur through SERCA2a nitration. We therefore investigated the role of SERCA2a nitration in heart failure. Methods and Results— We measured SERCA2a levels and nitrotyrosine levels in tissue from normal and failing human hearts using Western blots. We found that nitrotyrosine levels in idiopathic dilated cardiomyopathic (DCM) hearts were almost double those of control hearts in age-matched groups. Nitrotyrosine was dominantly present in a single protein with the molecular weight of SERCA2a, and immunoprecipitation confirmed that the protein recognized by the nitrotyrosine antibody was SERCA2a. There was a positive correlation between the time to half relaxation and the nitrotyrosine/SERCA2a content ( P Conclusions— We conclude that SERCA2a inactivation by nitration may contribute to Ca pump failure and hence heart failure in DCM. |
| Databáze: | OpenAIRE |
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