Cargando…
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...
Autores principales: | , , , , , , |
---|---|
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 |
_version_ | 1782242772107919360 |
---|---|
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. |
format | Online Article Text |
id | pubmed-3437290 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | International Scholarly Research Network |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT vasticecilia doxorubicinandnrg1erbb4deficiencyaffectgeneexpressionprofileinvolvingproteinhomeostasisinmouse AT witthenning doxorubicinandnrg1erbb4deficiencyaffectgeneexpressionprofileinvolvingproteinhomeostasisinmouse AT saidmatilde doxorubicinandnrg1erbb4deficiencyaffectgeneexpressionprofileinvolvingproteinhomeostasisinmouse AT sorrochepatricia doxorubicinandnrg1erbb4deficiencyaffectgeneexpressionprofileinvolvingproteinhomeostasisinmouse AT garciarivellohernan doxorubicinandnrg1erbb4deficiencyaffectgeneexpressionprofileinvolvingproteinhomeostasisinmouse AT ruiznoppingerpatricia doxorubicinandnrg1erbb4deficiencyaffectgeneexpressionprofileinvolvingproteinhomeostasisinmouse AT hertigceciliam doxorubicinandnrg1erbb4deficiencyaffectgeneexpressionprofileinvolvingproteinhomeostasisinmouse |