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...
| Autores: | , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2010 |
| País: | Argentina |
| Institución: | Consejo Nacional de Investigaciones Científicas y Técnicas |
| Repositorio: | CONICET Digital (CONICET) |
| Idioma: | inglés |
| OAI Identifier: | oai:ri.conicet.gov.ar:11336/143101 |
| Acceso en línea: | http://hdl.handle.net/11336/143101 |
| Access Level: | acceso abierto |
| Palabra clave: | Anrep effect EGFR Transactivation https://purl.org/becyt/ford/3.1 https://purl.org/becyt/ford/3 |
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The Anrep effect requires transactivation of the epidermal growth factor receptor |
| title |
The Anrep effect requires transactivation of the epidermal growth factor receptor |
| spellingShingle |
The Anrep effect requires transactivation of the epidermal growth factor receptor Villa-Abrille, María Celeste Anrep effect EGFR Transactivation https://purl.org/becyt/ford/3.1 https://purl.org/becyt/ford/3 |
| 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 |
The Anrep effect requires transactivation of the epidermal growth factor receptor |
| dc.creator.none.fl_str_mv |
Villa-Abrille, María Celeste Caldiz, Claudia Irma Ennis, Irene Lucia Nolly, Mariela Beatriz Casarini, María J. Chiappe, Gladys Ethel Cingolani, Horacio Eugenio Perez, Nestor Gustavo |
| author |
Villa-Abrille, María Celeste |
| author_facet |
Villa-Abrille, María Celeste Caldiz, Claudia Irma Ennis, Irene Lucia Nolly, Mariela Beatriz Casarini, María J. Chiappe, Gladys Ethel Cingolani, Horacio Eugenio Perez, Nestor Gustavo |
| author_role |
author |
| author2 |
Caldiz, Claudia Irma Ennis, Irene Lucia Nolly, Mariela Beatriz Casarini, María J. Chiappe, Gladys Ethel Cingolani, Horacio Eugenio Perez, Nestor Gustavo |
| author2_role |
author author author author author author author |
| dc.subject.none.fl_str_mv |
Anrep effect EGFR Transactivation https://purl.org/becyt/ford/3.1 https://purl.org/becyt/ford/3 |
| topic |
Anrep effect EGFR Transactivation https://purl.org/becyt/ford/3.1 https://purl.org/becyt/ford/3 |
| 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. © 2010 The Authors. Journal compilation © 2010 The Physiological Society. |
| publishDate |
2010 |
| dc.date.none.fl_str_mv |
2010-05 |
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info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://purl.org/coar/resource_type/c_6501 info:ar-repo/semantics/articulo |
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article |
| status_str |
publishedVersion |
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http://hdl.handle.net/11336/143101 Villa-Abrille, María Celeste; Caldiz, Claudia Irma; Ennis, Irene Lucia; Nolly, Mariela Beatriz; Casarini, María J.; et al.; The Anrep effect requires transactivation of the epidermal growth factor receptor; Wiley Blackwell Publishing, Inc; The Journal Of Physiology; 588; 9; 5-2010; 1579-1590 0022-3751 1469-7793 CONICET Digital CONICET |
| url |
http://hdl.handle.net/11336/143101 |
| identifier_str_mv |
Villa-Abrille, María Celeste; Caldiz, Claudia Irma; Ennis, Irene Lucia; Nolly, Mariela Beatriz; Casarini, María J.; et al.; The Anrep effect requires transactivation of the epidermal growth factor receptor; Wiley Blackwell Publishing, Inc; The Journal Of Physiology; 588; 9; 5-2010; 1579-1590 0022-3751 1469-7793 CONICET Digital CONICET |
| dc.language.none.fl_str_mv |
eng |
| language |
eng |
| dc.relation.none.fl_str_mv |
info:eu-repo/semantics/altIdentifier/doi/10.1113/jphysiol.2009.186619 info:eu-repo/semantics/altIdentifier/url/https://physoc.onlinelibrary.wiley.com/doi/10.1113/jphysiol.2009.186619 |
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info:eu-repo/semantics/openAccess https://creativecommons.org/licenses/by-nc-sa/2.5/ar/ |
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openAccess |
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https://creativecommons.org/licenses/by-nc-sa/2.5/ar/ |
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application/pdf application/pdf application/pdf application/pdf application/pdf application/pdf application/pdf |
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Wiley Blackwell Publishing, Inc |
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Wiley Blackwell Publishing, Inc |
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reponame:CONICET Digital (CONICET) instname:Consejo Nacional de Investigaciones Científicas y Técnicas |
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Consejo Nacional de Investigaciones Científicas y Técnicas |
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CONICET Digital (CONICET) |
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CONICET Digital (CONICET) |
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CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas |
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dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar |
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1799194626594177024 |
| spelling |
The Anrep effect requires transactivation of the epidermal growth factor receptorVilla-Abrille, María CelesteCaldiz, Claudia IrmaEnnis, Irene LuciaNolly, Mariela BeatrizCasarini, María J.Chiappe, Gladys EthelCingolani, Horacio EugenioPerez, Nestor GustavoAnrep effectEGFRTransactivationhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Myocardial 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. © 2010 The Authors. Journal compilation © 2010 The Physiological Society.Fil: Villa-Abrille, María Celeste. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani". Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; ArgentinaFil: Caldiz, Claudia Irma. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani". Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; ArgentinaFil: Ennis, Irene Lucia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani". Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; ArgentinaFil: Nolly, Mariela Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani". Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; ArgentinaFil: Casarini, María J.. Universidad Nacional de La Plata. Facultad de Ciencias Médicas; ArgentinaFil: Chiappe, Gladys Ethel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani". Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; ArgentinaFil: Cingolani, Horacio Eugenio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani". Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; ArgentinaFil: Perez, Nestor Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani". Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; ArgentinaWiley Blackwell Publishing, Inc2010-05info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/143101Villa-Abrille, María Celeste; Caldiz, Claudia Irma; Ennis, Irene Lucia; Nolly, Mariela Beatriz; Casarini, María J.; et al.; The Anrep effect requires transactivation of the epidermal growth factor receptor; Wiley Blackwell Publishing, Inc; The Journal Of Physiology; 588; 9; 5-2010; 1579-15900022-37511469-7793CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1113/jphysiol.2009.186619info:eu-repo/semantics/altIdentifier/url/https://physoc.onlinelibrary.wiley.com/doi/10.1113/jphysiol.2009.186619info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2024-05-08T13:33:02Zoai:ri.conicet.gov.ar:11336/143101instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982024-05-08 13:33:03.206CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
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15,81155 |