The role of CaMKII regulation of phospholamban activity in heart disease
Phospholamban (PLN) is a phosphoprotein in cardiac sarcoplasmic reticulum (SR) that is a reversible regulator of the Ca<sup>2+</sup>-ATPase (SERCA2a) activity and cardiac contractility. Dephosphorylated PLN inhibits SERCA2a and PLN phosphorylation, at either Ser<sup>16</sup>...
Guardado en:
| Autores principales: | , |
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| Formato: | Articulo Revision |
| Lenguaje: | Inglés |
| Publicado: |
2014
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| Acceso en línea: | http://sedici.unlp.edu.ar/handle/10915/85070 |
| Aporte de: |
| id |
I19-R120-10915-85070 |
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| record_format |
dspace |
| institution |
Universidad Nacional de La Plata |
| institution_str |
I-19 |
| repository_str |
R-120 |
| collection |
SEDICI (UNLP) |
| language |
Inglés |
| topic |
Ciencias Médicas Acidosis CaMKII Heart failure Ischemia/reperfusion injury Myocardium PLN regulation |
| spellingShingle |
Ciencias Médicas Acidosis CaMKII Heart failure Ischemia/reperfusion injury Myocardium PLN regulation Mattiazzi, Alicia Ramona Kranias, Evangelina G. The role of CaMKII regulation of phospholamban activity in heart disease |
| topic_facet |
Ciencias Médicas Acidosis CaMKII Heart failure Ischemia/reperfusion injury Myocardium PLN regulation |
| description |
Phospholamban (PLN) is a phosphoprotein in cardiac sarcoplasmic reticulum (SR) that is a reversible regulator of the Ca<sup>2+</sup>-ATPase (SERCA2a) activity and cardiac contractility. Dephosphorylated PLN inhibits SERCA2a and PLN phosphorylation, at either Ser<sup>16</sup> by PKA or Thr<SUP>17</SUP> by Ca<sup>2+</sup>-calmodulin-dependent protein kinase (CaMKII), reverses this inhibition. Through this mechanism, PLN is a key modulator of SR Ca<sup>2+</sup> uptake, Ca<sup>2+</sup> load, contractility, and relaxation. PLN phosphorylation is also the main determinant of ß1-adrenergic responses in the heart. Although phosphorylation of Thr<SUP>17</SUP> by CaMKII contributes to this effect, its role is subordinate to the PKA-dependent increase in cytosolic Ca<sup>2+</sup>, necessary to activate CaMKII. Furthermore, the effects of PLN and its phosphorylation on cardiac function are subject to additional regulation by its interacting partners, the anti-apoptotic HAX-1 protein and Gm or the anchoring unit of protein phosphatase 1. Regulation of PLN activity by this multimeric complex becomes even more important in pathological conditions, characterized by aberrant Ca<sup>2+</sup>-cycling. In this scenario, CaMKII-dependent PLN phosphorylation has been associated with protective effects in both acidosis and ischemia/reperfusion. However, the beneficial effects of increasing SR Ca<sup>2+</sup> uptake through PLN phosphorylation may be lost or even become deleterious, when these occur in association with alterations in SR Ca<sup>2+</sup> leak. Moreover, a major characteristic in human and experimental heart failure (HF) is depressed SR Ca<sup>2+</sup> uptake, associated with decreased SERCA2a levels and dephosphorylation of PLN, leading to decreased SR Ca<sup>2+</sup> load and impaired contractility. Thus, the strategy of altering SERCA2a and/or PLN levels or activity to restore perturbed SR Ca<sup>2+</sup> uptake is a potential therapeutic tool for HF treatment. We will review here the role of CaMKII-dependent phosphorylation of PLN at Thr<SUP>17</SUP> on cardiac function under physiological and pathological conditions. |
| format |
Articulo Revision |
| author |
Mattiazzi, Alicia Ramona Kranias, Evangelina G. |
| author_facet |
Mattiazzi, Alicia Ramona Kranias, Evangelina G. |
| author_sort |
Mattiazzi, Alicia Ramona |
| title |
The role of CaMKII regulation of phospholamban activity in heart disease |
| title_short |
The role of CaMKII regulation of phospholamban activity in heart disease |
| title_full |
The role of CaMKII regulation of phospholamban activity in heart disease |
| title_fullStr |
The role of CaMKII regulation of phospholamban activity in heart disease |
| title_full_unstemmed |
The role of CaMKII regulation of phospholamban activity in heart disease |
| title_sort |
role of camkii regulation of phospholamban activity in heart disease |
| publishDate |
2014 |
| url |
http://sedici.unlp.edu.ar/handle/10915/85070 |
| work_keys_str_mv |
AT mattiazzialiciaramona theroleofcamkiiregulationofphospholambanactivityinheartdisease AT kraniasevangelinag theroleofcamkiiregulationofphospholambanactivityinheartdisease AT mattiazzialiciaramona roleofcamkiiregulationofphospholambanactivityinheartdisease AT kraniasevangelinag roleofcamkiiregulationofphospholambanactivityinheartdisease |
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Repositorios |
| _version_ |
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