The Anrep effect requires transactivation of the epidermal growth factor receptor
Myocardial stretch elicits a biphasic contractile response: the Frank-Starling mechanism followed by the slow force response (SFR) or Anrep effect. In this study we hypothesized that the SFR depends on epidermal growth factor receptor (EGFR) transactivation after the myocardial stretch-induced angio...
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| Autores principales: | , , , , , , , |
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| Formato: | Articulo |
| Lenguaje: | Inglés |
| Publicado: |
2010
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| Acceso en línea: | http://sedici.unlp.edu.ar/handle/10915/82420 |
| Aporte de: |
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I19-R120-10915-82420 |
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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 Angiotensin II Animals Cats Endothelin-1 Extracellular Signal-Regulated MAP Kinases Mechanoreceptors Myocardial Contraction Oxidation-Reduction Papillary Muscles Phosphorylation Reactive Oxygen Species Receptor Cross-Talk Receptors, G-Protein-Coupled Reverse Transcriptase Polymerase Chain Reaction RNA |
| spellingShingle |
Ciencias Médicas Angiotensin II Animals Cats Endothelin-1 Extracellular Signal-Regulated MAP Kinases Mechanoreceptors Myocardial Contraction Oxidation-Reduction Papillary Muscles Phosphorylation Reactive Oxygen Species Receptor Cross-Talk Receptors, G-Protein-Coupled Reverse Transcriptase Polymerase Chain Reaction RNA Villa Abrille, María Celeste Caldiz, Claudia Irma Ennis, Irene Lucía Nolly, Mariela Casarini, María Jesús Chiappe de Cingolani, Gladys Ethel Cingolani, Horacio Eugenio Pérez, Néstor Gustavo The Anrep effect requires transactivation of the epidermal growth factor receptor |
| topic_facet |
Ciencias Médicas Angiotensin II Animals Cats Endothelin-1 Extracellular Signal-Regulated MAP Kinases Mechanoreceptors Myocardial Contraction Oxidation-Reduction Papillary Muscles Phosphorylation Reactive Oxygen Species Receptor Cross-Talk Receptors, G-Protein-Coupled Reverse Transcriptase Polymerase Chain Reaction RNA |
| description |
Myocardial stretch elicits a biphasic contractile response: the Frank-Starling mechanism followed by the slow force response (SFR) or Anrep effect. In this study we hypothesized that the SFR depends on epidermal growth factor receptor (EGFR) transactivation after the myocardial stretch-induced angiotensin II (Ang II)/endothelin (ET) release. Experiments were performed in isolated cat papillary muscles stretched from 92 to 98% of the length at which maximal twitch force was developed (Lmax). The SFR was 123 ± 1% of the immediate rapid phase (n = 6, P < 0.05) and was blunted by preventing EGFR transactivation with the Src-kinase inhibitor PP1 (99 ± 2%, n = 4), matrix metalloproteinase inhibitor MMPI (108 ± 4%, n = 11), the EGFR blocker AG1478 (98 ± 2%, n = 6) or the mitochondrial transition pore blocker clyclosporine (99 ± 3%, n = 6). Stretch increased ERK1/2 phosphorylation by 196 ± 17% of control (n = 7, P < 0.05), an effect that was prevented by PP1 (124 ± 22%, n = 7) and AG1478 (131 ± 17%, n = 4). In myocardial slices, Ang II (which enhances ET mRNA) or endothelin-1 (ET-1)-induced increase in O2- production (146 ± 14%, n = 9, and 191 ± 17%, n = 13, of control, respectively, P < 0.05) was cancelled by AG1478 (94 ± 5%, n = 12, and 98 ± 15%, n = 8, respectively) or PP1 (100 ± 4%, n = 6, and 99 ± 8%, n = 3, respectively). EGF increased O2- production by 149 ± 4% of control (n = 9, P < 0.05), an effect cancelled by inhibiting NADPH oxidase with apocynin (110 ± 6% n = 7), mKATP channels with 5-hydroxydecanoic acid (5-HD; 105 ± 5%, n = 8), the respiratory chain with rotenone (110 ± 7%, n = 7) or the mitochondrial permeability transition pore with cyclosporine (111 ± 10%, n = 6). EGF increased ERK1/2 phosphorylation (136 ± 8% of control, n = 9, P < 0.05), which was blunted by 5-HD (97 ± 5%, n = 4), suggesting that ERK1/2 activation is downstream of mitochondrial oxidative stress. Finally, stretch increased Ser703 Na+/H+ exchanger-1 (NHE-1) phosphorylation by 172 ± 24% of control (n = 4, P < 0.05), an effect that was cancelled by AG1478 (94 ± 17%, n = 4). In conclusion, our data show for the first time that EGFR transactivation is crucial in the chain of events leading to the Anrep effect. |
| format |
Articulo Articulo |
| author |
Villa Abrille, María Celeste Caldiz, Claudia Irma Ennis, Irene Lucía Nolly, Mariela Casarini, María Jesús Chiappe de Cingolani, Gladys Ethel Cingolani, Horacio Eugenio Pérez, Néstor Gustavo |
| author_facet |
Villa Abrille, María Celeste Caldiz, Claudia Irma Ennis, Irene Lucía Nolly, Mariela Casarini, María Jesús Chiappe de Cingolani, Gladys Ethel Cingolani, Horacio Eugenio Pérez, Néstor Gustavo |
| author_sort |
Villa Abrille, María Celeste |
| title |
The Anrep effect requires transactivation of the epidermal growth factor receptor |
| title_short |
The Anrep effect requires transactivation of the epidermal growth factor receptor |
| title_full |
The Anrep effect requires transactivation of the epidermal growth factor receptor |
| title_fullStr |
The Anrep effect requires transactivation of the epidermal growth factor receptor |
| title_full_unstemmed |
The Anrep effect requires transactivation of the epidermal growth factor receptor |
| title_sort |
anrep effect requires transactivation of the epidermal growth factor receptor |
| publishDate |
2010 |
| url |
http://sedici.unlp.edu.ar/handle/10915/82420 |
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