Open Access
Issue
Vet. Res.
Volume 41, Number 2, March–April 2010
Number of page(s) 14
DOI http://dx.doi.org/10.1051/vetres/2009063
Published online 23 October 2009
How to cite this article Vet. Res. (2010) 41:15
How to cite this article: Vet. Res. (2010) 41:15
DOI: 10.1051/vetres/2009063

Apoptosis induction in BEFV-infected Vero and MDBK cells through Src-dependent JNK activation regulates caspase-3 and mitochondria pathways

Chun-Yen Chen1, Chin-Yang Chang1, Hung-Jen Liu2, 3, Ming-Huei Liao2, 3, Chi-I Chang2, Jue-Liang Hsu2 and Wen-Ling Shih2

1  Graduate Institute and Department of Life Science, Tzu-Chi University, Hualien, Taiwan, Republic of China
2  Graduate Institute of Biotechnology, National Pingtung University of Science and Technology, 1, Shuefu Rd., Neipu, Pingtung, 91201, Taiwan, Republic of China
3  Department of Veterinary Medicine, National Pingtung University of Science and Technology, Pingtung, Taiwan, Republic of China

Published online: 23 October 2009

Abstract - Our previous report demonstrated that bovine ephemeral fever virus (BEFV)-infected cultured cells could induce caspase-dependent apoptosis. This study aims to further elucidate how BEFV activates the caspase cascade in bovine cells. BEFV replicated and induced apoptosis in Vero and Madin-Darby bovine kidney (MDBK) cells, and a kinetic study showed a higher efficiency of replication and a greater apoptosis induction ability of BEFV in Vero cells. Src and c-Jun N-terminal kinase (JNK) inhibitor, but not extracellular signal-regulated kinase (ERK) or p38 inhibitor, alleviated BEFV-mediated cytopathic effect and apoptosis. In BEFV-infected Vero and MDBK cells, BEFV directly induced Src tyrosine-418 phosphorylation and JNK phosphorylation and kinase activity, which was inhibited specifically by SU6656 and SP600125, respectively. The caspase cascade and its downstream effectors, Poly (ADP-ribose) polymerase (PARP) and DFF45, were also activated simultaneously upon BEFV infection. In addition, cytochrome c, but not Smac/DIABLO, was released gradually from mitochondria after BEFV infection. SU6656 suppressed Src, JNK, and caspase-3 and -9 activation, as well as PARP and DFF45 cleavage; SP600125 reduced JNK and caspase-3 and -9 activation, as well as PARP and DFF45 cleavage. Taken together, these results strongly support the hypothesis that a Src-dependent JNK signaling pathway plays a key role in BEFV-induced apoptosis. The molecular mechanism identified in our study may provide useful information for the treatment of BEFV.


Key words: BEFV / apoptosis / caspase / Src / JNK

Corresponding author: wlshih@mail.npust.edu.tw

© INRA, EDP Sciences 2009