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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Veröffentlicht in:ISRN Cardiology 2012, Vol.2012 (2012), p.1-11
Hauptverfasser: Vasti, Cecilia, Witt, Henning, Said, Matilde, Sorroche, Patricia, García-Rivello, Hernán, Ruiz-Noppinger, Patricia, Hertig, Cecilia M.
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Sprache:eng
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Zusammenfassung: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.
ISSN:2090-5580
2090-5599
2090-5599
DOI:10.5402/2012/745185