Doxorubicin and NRG-1/erbB4-Deficiency Affect Gene Expression Profile: Involving Protein Homeostasis in Mouse

The accumulating evidence demonstrates the essential role of neuregulin-1 signaling in the adult heart, and, moreover, indicates that an impaired neuregulin signaling exacerbates the doxorubicin-mediated cardiac toxicity. Despite this strong data, the specific cardiomyocyte targets of the active erb...

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Autores principales: Vasti, Cecilia, Witt, Henning, Said, María Matilde, Sorroche, Patricia, García Rivello, Hernán Jorge, Ruiz Noppinger, Patricia, Hertig, Cecilia M.
Formato: Articulo
Lenguaje:Inglés
Publicado: 2012
Materias:
Ciencias Médicas
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/124514
Aporte de:
SEDICI (UNLP) de Universidad Nacional de La Plata
id I19-R120-10915-124514
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
spellingShingle Ciencias Médicas
Vasti, Cecilia
Witt, Henning
Said, María Matilde
Sorroche, Patricia
García Rivello, Hernán Jorge
Ruiz Noppinger, Patricia
Hertig, Cecilia M.
Doxorubicin and NRG-1/erbB4-Deficiency Affect Gene Expression Profile: Involving Protein Homeostasis in Mouse
topic_facet Ciencias Médicas
description The accumulating evidence demonstrates the essential role of neuregulin-1 signaling in the adult heart, and, moreover, indicates that an impaired neuregulin signaling exacerbates the doxorubicin-mediated cardiac toxicity. Despite this strong data, the specific cardiomyocyte targets of the active erbB2/erbB4 heterodimer remain unknown. In this paper, we examined pathways involved in cardiomyocyte damage as a result of the cardiac sensitization to anthracycline toxicity in the ventricular muscle-specific erbB4 knockout mouse. We performed morphological analyses to evaluate the ventricular remodeling and employed a cDNA microarray to assess the characteristic gene expression profile, verified data by real-time RT-PCR, and then grouped into functional categories and pathways. We confirm the upregulation of genes related to the classical signature of a hypertrophic response, implicating an erbB2-dependent mechanism in doxorubicin-treated erbB4-KO hearts. Our results indicate the remarkable downregulation of IGF-I/PI-3′ kinase pathway and extends our current knowledge by uncovering an altered ubiquitin-proteasome system leading to cardiomyocyte autophagic vacuolization.
format Articulo
Articulo
author Vasti, Cecilia
Witt, Henning
Said, María Matilde
Sorroche, Patricia
García Rivello, Hernán Jorge
Ruiz Noppinger, Patricia
Hertig, Cecilia M.
author_facet Vasti, Cecilia
Witt, Henning
Said, María Matilde
Sorroche, Patricia
García Rivello, Hernán Jorge
Ruiz Noppinger, Patricia
Hertig, Cecilia M.
author_sort Vasti, Cecilia
title Doxorubicin and NRG-1/erbB4-Deficiency Affect Gene Expression Profile: Involving Protein Homeostasis in Mouse
title_short Doxorubicin and NRG-1/erbB4-Deficiency Affect Gene Expression Profile: Involving Protein Homeostasis in Mouse
title_full Doxorubicin and NRG-1/erbB4-Deficiency Affect Gene Expression Profile: Involving Protein Homeostasis in Mouse
title_fullStr Doxorubicin and NRG-1/erbB4-Deficiency Affect Gene Expression Profile: Involving Protein Homeostasis in Mouse
title_full_unstemmed Doxorubicin and NRG-1/erbB4-Deficiency Affect Gene Expression Profile: Involving Protein Homeostasis in Mouse
title_sort doxorubicin and nrg-1/erbb4-deficiency affect gene expression profile: involving protein homeostasis in mouse
publishDate 2012
url http://sedici.unlp.edu.ar/handle/10915/124514
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bdutipo_str Repositorios
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