About this Journal Submit a Manuscript Table of Contents
BioMed Research International
Volume 2013 (2013), Article ID 845816, 9 pages
http://dx.doi.org/10.1155/2013/845816
Research Article

A New Dual-Promoter System for Cardiomyocyte-Specific Conditional Induction of Apoptosis

1Gruppo Intini-SMA Laboratory of Experimental Cardiology, Institute of Life Sciences, Scuola Superiore Sant’Anna, 56127 Pisa, Italy
2Retrovirus Centre and Virology Section, Department of Translational Research, University of Pisa, 56127 Pisa, Italy
3Molecular Medicine Laboratory, International Centre for Genetic Engineering and Biotechnology, Padriciano, 34149 Trieste, Italy
4Department of Physiology, Temple University School of Medicine, Philadelphia, PA 19140, USA

Received 2 October 2012; Accepted 13 December 2012

Academic Editor: Decheng Yang

Copyright © 2013 Silvia Agostini et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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+-Ca2+ 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.