Epac in cardiac calcium signaling
| Autor: | Anna Llach, Jean-Pierre Benitah, Alejandro Domínguez-Rodríguez, Frank Lezoualc'h, Eric Morel, Gema Ruiz-Hurtado, Ana María Gómez |
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| Přispěvatelé: | Signalisation et physiopathologie cardiaque, Université Paris-Sud - Paris 11 (UP11)-IFR141-Institut National de la Santé et de la Recherche Médicale (INSERM), Unidad de Hipertensión, Hospital 12 de Octubre-Instituto de Investigación imas12, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Simon, Marie Francoise |
| Rok vydání: | 2013 |
| Předmět: |
Mef2
medicine.medical_specialty [SDV.BC]Life Sciences [q-bio]/Cellular Biology 030204 cardiovascular system & hematology MESH: Calcium Signaling MESH: Ryanodine Receptor Calcium Release Channel 03 medical and health sciences 0302 clinical medicine Stress Physiological MESH: Excitation Contraction Coupling Internal medicine Ca2+/calmodulin-dependent protein kinase Cyclic AMP medicine Animals Guanine Nucleotide Exchange Factors Humans MESH: Guanine Nucleotide Exchange Factors Myocyte MESH: Animals Calcium Signaling MESH: Stress Physiological [SDV.BC] Life Sciences [q-bio]/Cellular Biology Molecular Biology Excitation Contraction Coupling MESH: Cyclic AMP 030304 developmental biology Calcium signaling 0303 health sciences MESH: Humans Phospholipase C Chemistry Ryanodine receptor Endoplasmic reticulum Ryanodine Receptor Calcium Release Channel Cell biology Sarcoplasmic Reticulum Endocrinology Type C Phospholipases MESH: Calcium MESH: Calcium-Calmodulin-Dependent Protein Kinase Type 2 MESH: Sarcoplasmic Reticulum Phosphorylation Calcium MESH: Type C Phospholipases Calcium-Calmodulin-Dependent Protein Kinase Type 2 Cardiology and Cardiovascular Medicine |
| Zdroj: | Journal of Molecular and Cellular Cardiology Journal of Molecular and Cellular Cardiology, Elsevier, 2013, 58, pp.162-71. ⟨10.1016/j.yjmcc.2012.11.021⟩ Journal of Molecular and Cellular Cardiology, 2013, 58, pp.162-71. ⟨10.1016/j.yjmcc.2012.11.021⟩ |
| ISSN: | 0022-2828 1095-8584 |
| DOI: | 10.1016/j.yjmcc.2012.11.021 |
| Popis: | Epac, exchange protein directly activated by cAMP, is emerging as a new regulator of cardiac physiopathology. Although its effects are much less known than the classical cAMP effector, PKA, several studies have investigated the cardiac role of Epac, providing evidences that Epac modulates intracellular Ca 2 + . In one of the first analyses, it was shown that Epac can increase the frequency of spontaneous Ca 2 + oscillations in cultured rat cardiomyocytes. Later on, in adult cardiomyocytes, it was shown that Epac can induce sarcoplasmic reticulum (SR) Ca 2 + release in a PKA independent manner. The pathway identified involved phospholipase C (PLC) and Ca 2 + /calmodulin kinase II (CaMKII). The latter phosphorylates the ryanodine receptor (RyR), increasing the Ca 2 + spark probability. The RyR, Ca 2 + release channel located in the SR membrane, is a key element in the excitation–contraction coupling. Thus Epac participates in the excitation–contraction coupling. Moreover, by inducing RyR phosphorylation, Epac is arrhythmogenic. A detailed analysis of Ca 2 + mobilization in different microdomains showed that Epac preferently elevated Ca 2 + in the nucleoplasm ([Ca 2 + ] n ). This effect, besides PLC and CaMKII, required inositol 1,4,5 trisphosphate receptor (IP 3 R) activation. IP 3 R is other Ca 2 + release channel located mainly in the perinuclear area in the adult ventricular myocytes, where it has been shown to participate in the excitation–transcription coupling (the process by which Ca 2 + activates transcription). If Epac activation is maintained for some time, the histone deacetylase (HDAC) is translocated out of the nucleus de-repressing the transcription factor myocyte enhancer factor (MEF2). These evidences also pointed to Epac role in activating the excitation–transcription coupling. In fact, it has been shown that Epac induces cardiomyocyte hypertrophy. Epac activation for several hours, even before the cell hypertrophies, induces a profound modulation of the excitation–contraction coupling: increasing the [Ca 2 + ] i transient amplitude and cellular contraction. Thus Epac actions are rapid but time and microdomain dependent in the cardiac myocyte. Taken together the results collected indicate that Epac may have an important role in the cardiac response to stress. This article is part of a Special Issue entitled "Calcium Signaling in Heart". |
| Databáze: | OpenAIRE |
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