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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, Matilde, Sorroche, Patricia, García-Rivello, Hernán, Ruiz-Noppinger, Patricia, Hertig, Cecilia M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: International Scholarly Research Network 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3437290/
https://www.ncbi.nlm.nih.gov/pubmed/22970387
http://dx.doi.org/10.5402/2012/745185
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author Vasti, Cecilia
Witt, Henning
Said, Matilde
Sorroche, Patricia
García-Rivello, Hernán
Ruiz-Noppinger, Patricia
Hertig, Cecilia M.
author_facet Vasti, Cecilia
Witt, Henning
Said, Matilde
Sorroche, Patricia
García-Rivello, Hernán
Ruiz-Noppinger, Patricia
Hertig, Cecilia M.
author_sort Vasti, Cecilia
collection PubMed
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.
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spelling pubmed-34372902012-09-11 Doxorubicin and NRG-1/erbB4-Deficiency Affect Gene Expression Profile: Involving Protein Homeostasis in Mouse Vasti, Cecilia Witt, Henning Said, Matilde Sorroche, Patricia García-Rivello, Hernán Ruiz-Noppinger, Patricia Hertig, Cecilia M. ISRN Cardiol Research Article 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. International Scholarly Research Network 2012-08-29 /pmc/articles/PMC3437290/ /pubmed/22970387 http://dx.doi.org/10.5402/2012/745185 Text en Copyright © 2012 Cecilia Vasti et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Vasti, Cecilia
Witt, Henning
Said, Matilde
Sorroche, Patricia
García-Rivello, Hernán
Ruiz-Noppinger, Patricia
Hertig, Cecilia M.
Doxorubicin and NRG-1/erbB4-Deficiency Affect Gene Expression Profile: Involving Protein Homeostasis in Mouse
title 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_short 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
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3437290/
https://www.ncbi.nlm.nih.gov/pubmed/22970387
http://dx.doi.org/10.5402/2012/745185
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