Padua Research Archive, l’archivio istituzionale della produzione scientifica dell’Università degli Studi di Padova, ha lo scopo di raccogliere, documentare, conservare e pubblicare, anche ad accesso aperto, i prodotti della ricerca dell’Ateneo. Padua Research Archive utilizza la piattaforma IRIS (Institutional Research Information System) sviluppata da Cineca.
EnglishBDNF and its associated tropomyosin-related kinase receptor B (TrkB) nurture vessels and nerves serving the heart. However, the direct effect of BDNF/TrkB signaling on the myocardium is poorly understood. Here we report that cardiac-specific TrkB knockout mice (TrkB(-/-)) display impaired cardiac contraction and relaxation, showing that BDNF/TrkB signaling acts constitutively to sustain in vivo myocardial performance. BDNF enhances normal cardiomyocyte Ca(2+) cycling, contractility, and relaxation via Ca(2+)/calmodulin-dependent protein kinase II (CaMKII). Conversely, failing myocytes, which have increased truncated TrkB lacking tyrosine kinase activity and chronically activated CaMKII, are insensitive to BDNF. Thus, BDNF/TrkB signaling represents a previously unidentified pathway by which the peripheral nervous system directly and tonically influences myocardial function in parallel with β-adrenergic control. Deficits in this system are likely additional contributors to acute and chronic cardiac dysfunction.
| Titolo: | Constitutive BDNF/TrkB signaling is required for normal cardiac contraction and relaxation (Proc Natl Acad Sci USA (2015) 112 (1880-1885) DOI: 10.1073/pnas.1504270112) | |
| Autori: | PAOLOCCI, NAZARENO (Corresponding) | |
| Data di pubblicazione: | 2015 | |
| Rivista: | ||
| Abstract: | BDNF and its associated tropomyosin-related kinase receptor B (TrkB) nurture vessels and nerves serving the heart. However, the direct effect of BDNF/TrkB signaling on the myocardium is poorly understood. Here we report that cardiac-specific TrkB knockout mice (TrkB(-/-)) display impaired cardiac contraction and relaxation, showing that BDNF/TrkB signaling acts constitutively to sustain in vivo myocardial performance. BDNF enhances normal cardiomyocyte Ca(2+) cycling, contractility, and relaxation via Ca(2+)/calmodulin-dependent protein kinase II (CaMKII). Conversely, failing myocytes, which have increased truncated TrkB lacking tyrosine kinase activity and chronically activated CaMKII, are insensitive to BDNF. Thus, BDNF/TrkB signaling represents a previously unidentified pathway by which the peripheral nervous system directly and tonically influences myocardial function in parallel with β-adrenergic control. Deficits in this system are likely additional contributors to acute and chronic cardiac dysfunction. | |
| Handle: | http://hdl.handle.net/11577/3288294 | |
| Appare nelle tipologie: | 01.01 - Articolo in rivista |
File in questo prodotto:
Pubblicazioni consigliate
Copyright © 2022