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

VASTI C; HENNING WITT; SAID M

ISRN Cardiol

Hindawi Publishing

Lugar: Cairo; Año: 2012 vol. 2012 p. 1 - 11

2090-5580

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 study, 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 and 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