title: Doxorubicin and NRG-1/erbB4-Deficiency Affect Gene Expression Profile: Involving Protein Homeostasis in Mouse.
abstract: 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.
authors.affiliation: Instituto de Investigaciones en Ingeniería Genética y Biología Molecular-(INGEBI), Vuelta de Obligado 2490, Buenos Aires 1428, Argentina.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Vasti
authors.forename: Henning
authors.initials: H
authors.lastname: Witt
authors.forename: Matilde
authors.initials: M
authors.lastname: Said
authors.forename: Patricia
authors.initials: P
authors.lastname: Sorroche
authors.forename: Hernán
authors.initials: H
authors.lastname: García-Rivello
authors.forename: Patricia
authors.initials: P
authors.lastname: Ruiz-Noppinger
authors.forename: Cecilia M
authors.initials: CM
authors.lastname: Hertig