A New Dual-Promoter System for Cardiomyocyte-Specific Conditional Induction of Apoptosis. (17th January 2013)

• Record Type: Journal Article
• Authors: Agostini, Silvia; Lionetti, Vincenzo; Matteucci, Marco; Chiuppesi, Flavia; Giacca, Mauro; Pistello, Mauro; Recchia, Fabio A.
• Other Names: Yang Decheng Academic Editor.
• Is Part Of: BioMed research international. Volume 2013(2013)
• Publication Date: 2013-01-17
• Subjects: Medicine -- Periodicals; Biology -- Periodicals; Biotechnology -- Periodicals; Life sciences -- Periodicals; 610.5
• DOI: 10.1155/2013/845816
• Languages: English
• ISSNs: 2314-6133

Abstract

Abstract : 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 used the cardiomyocyte-specific Na + -Ca 2+ exchange promoter to control the transcription of the reverse tetracycline transactivator, while the transgene expression was driven by the tetracycline-responsive element. The proapoptotic 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 tetracycline-regulated induction of apoptosis, which was not observed in noncardiac cells. Therefore, our system proved a valuable molecular tool for inducing controlled apoptosis in selected cells. Furthermore, the vector we developed is suitable for "lentivirus transgenesis, " an interesting strategy recently proposed for the genetic manipulation of animals other than mice, including large mammals.