Bid cleavage, cytochrome c release and caspase activation in canine coronavirus-induced apoptosis.

Bid cleavage, cytochrome c release and caspase activation in canine coronavirus-induced apoptosis.
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DOI:
10.1016/j.vetmic.2009.09.001
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发表时间:
2010-02-24
影响因子:
3.3
通讯作者:
Pagnini U
Pagnini U
中科院分区:
农林科学2区
文献类型:
--
作者:
De Martino L;Marfé G;Longo M;Fiorito F;Montagnaro S;Iovane V;Decaro N;Pagnini U

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先前的研究表明,犬冠状病毒(CCoV)感染犬纤维肉瘤细胞系(A-72细胞)导致细胞凋亡。在这项研究中,我们研究了感染过程中的细胞死亡过程及其机制。我们发现CCoV-II通过激活启动子(caspase-8和-9)和执行子(caspase-3和-6)caspase来触发A-72细胞的凋亡。聚(ADP-核糖)聚合酶(PARP)的蛋白水解裂解证实了执行caspase的激活。此外,CCoV-II感染导致截短的bid(tbid)易位从胞质到线粒体的部分,细胞色素c从线粒体的释放,并在bcl-2家族的促凋亡和抗凋亡蛋白的改变。我们的数据表明,在这个实验模型中,内在和外在途径都参与。此外,我们证明了半胱天冬酶抑制剂对细胞凋亡的抑制并不影响CCoV的复制,这表明细胞凋亡在促进病毒释放方面不起作用。
A previous study demonstrated that infection of a canine fibrosarcoma cell line (A-72 cells) by canine coronavirus (CCoV) resulted in apoptosis. In this study, we investigated the cell death processes during infection and the underlying mechanisms. We found that CCoV-II triggers apoptosis in A-72 cells by activating initiator (caspase-8 and -9) and executioner (caspase-3 and -6) caspases. The proteolytic cleavage of poly(ADP-ribose) polymerases (PARPs) confirmed the activation of executioner caspases. Furthermore, CCoV-II infection resulted in truncated bid (tbid) translocation from the cytosolic to the mitochondrial fraction, the cytochrome c release from mitochondria, and alterations in the pro- and anti-apoptotic proteins of bcl-2 family. Our data indicated that, in this experimental model, both intrinsic and extrinsic pathways are involved. In addition, we demonstrated that the inhibition of apoptosis by caspase inhibitors did not affect CCoV replication, suggesting that apoptosis does not play a role in facilitating viral release.
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