title: Porcine parvovirus infection activates mitochondria-mediated apoptotic signaling pathway by inducing ROS accumulation.
abstract: BACKGROUND
  Porcine parvovirus (PPV) infection primarily causes reproductive failure of pregnant swine and results in host cell death. Boars, as an important disseminator, shed PPV to sows via semen. PPV infects and numerously replicates in boar testicle, which results in damage of swine testicle in vivo. Reactive oxygen species (ROS), a mediator of cell apoptosis, play a crucial role in the mitochondria apoptotic pathway. However, whether PPV infection induces ST cells apoptosis and ROS accumulation is still unclear.
  
  
  METHODS
  To determine the effects of PPV infection on the apoptosis, we detected morphological changes, DNA ladder, activities of caspases, and expression of PARP in PPV-infected ST cells. Moreover, aiming to investigate the effect of PPV infection on the mitochondrial apoptotic pathway and ROS accumulation, we detected the Δψm, apoptosis-related genes, and ROS. To investigate the role of ROS in the process of PPV-induced apoptosis, the ST cells were infected with PPV and treated with the ROS antioxidants. The ROS level was measured using Reactive Oxygen Species Assay Kit and the Δψm, expression level of Bcl-2, translocation of Bax, and redistribution of mitochondria cytochrome c were tested.
  
  
  RESULTS
  In this study, we demonstrated that PPV infection could induce apoptosis that was characterized by morphological changes, DNA fragmentation and activation of caspases. Moreover, PPV infection suppressed Bcl-2 expression, enhanced Bax expression and translocation to mitochondria, decreased the mitochondrial transmembrane potential, and triggered the release of cytochrome c, which caused the subsequent activation of caspase-9 and caspase-3 and initiation of apoptosis. However, during the process of PPV-induced apoptosis, the protein levels of Fas and FasL were not affected. Further studies showed that PPV infection caused ROS accumulation. Inhibition of ROS could reduce mitochondrial transmembrane potential and could significantly block ST cells apoptosis via suppressing Bax translocation, cytochrome c and caspase-3 activation.
  
  
  CONCLUSIONS
  All these results suggest that PPV-induced ROS accumulation mediates apoptosis in ST cells, which provided theoretical basis for the molecular pathogenesis of PPV infection.
authors.affiliation: College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, 712100, People's Republic of China. xiaominz2012@163.com.
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Zhao
authors.affiliation: College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, 712100, People's Republic of China. xhl0610@163.com.
authors.forename: Hailing
authors.initials: H
authors.lastname: Xiang
authors.affiliation: College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, 712100, People's Republic of China. bxybxy1014@163.com.
authors.forename: Xiaoyuan
authors.initials: X
authors.lastname: Bai
authors.affiliation: College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, 712100, People's Republic of China. 396726686@qq.com.
authors.forename: Naijiao
authors.initials: N
authors.lastname: Fei
authors.affiliation: College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, 712100, People's Republic of China. huangyong@nwsuaf.edu.cn.
authors.forename: Yong
authors.initials: Y
authors.lastname: Huang
authors.affiliation: College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, 712100, People's Republic of China. songxiangjun1007@126.com.
authors.forename: Xiangjun
authors.initials: X
authors.lastname: Song
authors.affiliation: College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, 712100, People's Republic of China. ready866281@163.com.
authors.forename: Hongling
authors.initials: H
authors.lastname: Zhang
authors.affiliation: College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, 712100, People's Republic of China. zhanglianghappyus@163.com.
authors.forename: Liang
authors.initials: L
authors.lastname: Zhang
authors.affiliation: College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, 712100, People's Republic of China. dwtong@nwsuaf.edu.cn.
authors.forename: Dewen
authors.initials: D
authors.lastname: Tong
mesh_terms: D000818:Animals; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002478:Cells, Cultured; D008297:Male; D053078:Membrane Potential, Mitochondrial; D008928:Mitochondria / Q000378:metabolism*; D010322:Parvoviridae Infections / Q000662:veterinary; D028323:Parvovirus, Porcine / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction; D013552:Swine; D013553:Swine Diseases / Q000378:metabolism / Q000821:virology; D013737:Testis / Q000166:cytology / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D053148:Caspase 3; D053453:Caspase 9