Apoptosis is a key determinant of major pathological processes, including chronic cardiac failure. We developed and tested in vitro a novel system to induce cardiomyocyte-specific apoptosis by virus-mediated delivery of a conditional transgene. The entire system was packaged in a lentiviral vector. We placed the cardiomyocyte-specific Na+-Ca2+ exchanger promoter to control the transcription of the reverse Tet transactivator, while the transgene expression was driven by the Tet-Responsive Element. The pro-apoptotic transgene of choice was the short isoform of the apoptosis–inducing factor, known to quickly induce the caspase-independent apoptosis when overexpressed in cells. Transduction of cardiomyocyte cells with this vector caused a Tet-regulated induction of apoptosis, which was not observed in non-cardiac cells. Therefore, our system proved a valuable molecular tool for inducing controlled apoptosis in selected cells. Further, the vector we developed is well-suited for “lentivirus trangenesis”, an interesting strategy recently proposed for the genetic manipulation of animals other than mice, including large mammals.
|Autori interni:||PISTELLO, MAURO|
|Autori:||Agostini S.; Lionetti V.; Matteucci M.; Chiuppesi F.; Giacca M.; Pistello M.; Recchia F.|
|Titolo:||A New Dual-Promoter System for Cardiomyocyte-Specific Conditional Induction of Apoptosis|
|Anno del prodotto:||2013|
|Digital Object Identifier (DOI):||10.1155/2013/845816|
|Appare nelle tipologie:||1.1 Articolo in rivista|