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

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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Main Authors: Vasti, Cecilia, Witt, Henning, Said, Matilde, Sorroche, Patricia, García-Rivello, Hernán, Ruiz-Noppinger, Patricia, Hertig, Cecilia M.
Format: Online
Language:English
Published: International Scholarly Research Network 2012
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3437290/
id pubmed-3437290
recordtype oai_dc
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. 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.
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Vasti, Cecilia
Witt, Henning
Said, Matilde
Sorroche, Patricia
García-Rivello, Hernán
Ruiz-Noppinger, Patricia
Hertig, Cecilia M.
spellingShingle 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
author_facet Vasti, Cecilia
Witt, Henning
Said, Matilde
Sorroche, Patricia
García-Rivello, Hernán
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
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.
publisher International Scholarly Research Network
publishDate 2012
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3437290/
_version_ 1611555271823327232

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