PERSONAL DE APOYO
BONANNO Marina Soledad
congresos y reuniones científicas
Título:
Neuregulin-1 Modulates Doxorubicin Cardiotoxicity In Mouse
Autor/es:
BONANNO, MARINA; PEREZ ABRAHAM, ABIGAIL; RIZZO, AGUSTÍN; GARCÍA RIVELLO, HERNÁN; HERTIG, CECILIA
Lugar:
CABA
Reunión:
Congreso; ISHR International Word Congress: Unraveling the mysteries of the heart at the rhythm of Tango; 2016
Institución organizadora:
ISHR
Resumen:
Neuregulin-1 (NRG1) signaling through tyrosine kinasereceptors erbB2 and erbB4 is required for cardiac morphogenesis, and plays anessential role in maintaining the myocardial architecture during adulthood.Targeted immunotherapies blocking the survival of erbB2+ cancer cells revealedthat an impaired NRG1 signal under anthracycline chemotherapy may lead todilated cardiomyopathy in a subpopulation of treated patients. Theventricular-specific deletion of ErbB4 (erbB4-KO) manifested dilatedcardiomyopathy, aggravated by the administration of anthracyclines(doxorubicin) (KOD). The exacerbated toxicity in KOD induced genes of theubiquitin-proteasome system and autophagy. Myofibril proteins were largelyubiquitinated with the commonality of a subgroup of proteins in the erbB4-KOand the doxorubicin mice WTD. We aimed to investigate the activities underlyingcardiomyocyte damage and moreover, to evaluate the therapeutic effect ofrecombinant NRG1βpeptides. We first examined biomarkers of apoptosis and autophagy (e.g. activecaspase3, LC3II/I), then characterized the ubiquitination profile of myofibrilsin 2D gels towards the monitoring of the rNRG1β effect through the reversion of the molecularmodifications observed in cardiotoxic conditions. We have identified newconsistent biomarkers of pathology and suggest that rNRG1β protects from cardiotoxic injury. </div></div></body></html>