Regulation of ROS in transmissible gastroenteritis virus-activated apoptotic signaling.
Transmissible gastroenteritis virus (TGEV), an enteropathogenic coronavirus, causes severe lethal watery diarrhea and dehydration in piglets. Previous studies indicate that TGEV infection induces cell apoptosis in host cells. In this study, we investigated the roles and regulation of reactive oxygen species (ROS) in TGEV-activated apoptotic signaling. The results showed that TGEV infection induced ROS accumulation, whereas UV-irradiated TGEV did not promote ROS accumulation. In addition, TGEV infection lowered mitochondrial transmembrane potential in PK-15 cell line, which could be inhibited by ROS scavengers, pyrrolidinedithiocarbamic (PDTC) and N-acetyl-l-cysteine (NAC). Furthermore, the two scavengers significantly inhibited the activation of p38 MAPK and p53 and further blocked apoptosis occurrence through suppressing the TGEV-induced Bcl-2 reduction, Bax redistribution, cytochrome c release and caspase-3 activation. These results suggest that oxidative stress pathway might be a key element in TGEV-induced apoptosis and TGEV pathogenesis.
College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi 712100, PR China; College of Life Sciences, Hainan Normal University, Haikou, Hainan 571158, PR China.
Li
L
Ding
Xiaomin
X
Zhao
Yong
Y
Huang
Qian
Q
Du
Feng
F
Dong
Hongling
H
Zhang
Xiangjun
X
Song
Wenlong
W
Zhang
Dewen
D
Tong
D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D016166:Free Radical Scavengers / Q000494:pharmacology; D005761:Gastroenteritis, Transmissible, of Swine / Q000378:metabolism* / Q000473:pathology* / Q000821:virology; D053078:Membrane Potential, Mitochondrial; D018384:Oxidative Stress; D011759:Pyrrolidines / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction; D013552:Swine; D013859:Thiocarbamates / Q000494:pharmacology; D005760:Transmissible gastroenteritis virus / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D016166:Free Radical Scavengers; D011759:Pyrrolidines; D017382:Reactive Oxygen Species; D013859:Thiocarbamates; D016159:Tumor Suppressor Protein p53; C020972:pyrrolidine dithiocarbamic acid; D048051:p38 Mitogen-Activated Protein Kinases; D000111:Acetylcysteine
Apoptosis; Mitochondrial transmembrane potential; ROS; TGEV