p53- and ROS-mediated AIF pathway involved in TGEV-induced apoptosis

The Journal of Veterinary Medical Science

Weihao LI¹  Li DING²  Jiawei LI³ 

[1] Hainan Entry-Exit Inspection and Quarantine Bureau, Haikou, Hainan 570311, China;Ministry of Education Key Laboratory for Ecology of Tropical Islands, College of Life Sciences, Hainan Normal University, Haikou 571158, China;School of Tropical Agricultural Technology, Hainan College of Vocation and Technique, Haikou, Hainan 570216, China

关键词: AIF;    apoptosis;    p53;    ROS;    TGEV;   

DOI  :  10.1292/jvms.18-0104

学科分类：兽医学

来源: Japanese Society of Veterinary Science

【 摘 要 】

We previously demonstrated that transmissible gastroenteritis virus (TGEV) could induce apoptosis through caspase signaling. However, apoptosis was not completely prevented by caspases inhibitors, suggesting that there may be a caspase-independent pathway involved in TGEV-induced cell apoptosis. In this study, we investigated the regulation of apoptosis-inducing factor (AIF) on TGEV-induced apoptotic pathway. Results indicated that AIF translocated from the mitochondria to nucleus during TGEV infection, and the AIF inhibitor, N-phenylmaleimide (NP), significantly attenuated the apoptosis. In addition, the translocation of AIF was inhibited by Veliparib (ABT-888), an inhibitor of poly (ADP-ribose) polymerase (PARP). And the reactive oxygen species (ROS) scavenger, pyrrolidinedithiocarbamic (PDTC), redistributed AIF in the mitochondria and nucleus in TGEV-infected cells. Moreover, the protein levels in nucleus and the mRNA levels of AIF were inhibited in the presence of the p53 inhibitor, pifithrin-α (PFT-α) or in TGEV-infected p53−/−cells. Furthermore, TGEV-induced apoptosis was blocked by combination of three or more inhibitors, such as pan caspase inhibitor Z-VAD-FMK, NP, ABT-888, PDTC, PFT-α, to treat PK-15 cells. Taken together, these results suggest that the p53- and ROS-mediated AIF pathway and caspase-dependent pathway were involved in TGEV-induced apoptosis.

【 授权许可】

Unknown