Nuclear-factor-kappaB (NF-kappaB) and radical oxygen species play contrary roles in transforming growth factor-beta1 (TGF-beta1)-induced apoptosis in hepatocellular carcinoma (HCC) cells.
Nuclear-Factor-kappaB (NF-kappaBeta can counteract transforming growth factor-beta1 (TGF-beta1)-induced apoptosis in malignant hepatocytes through up-regulation of its downstream genes, such as X-linked inhibitor of apoptosis protein (XIAP). Reports have demonstrated that TGF-beta1 can induce oxidative stress, and c-Jun N-terminal Kinase1 (JNK1) is indispensable for TGF-beta1-induced apoptosis pathway, but the relationship between radical oxygen species (ROS) and the activation of JNKs is still unclear. In the present study, we found that ROS can induce JNK activation in TGF-beta1 mediated apoptosis in hepatocytes. The inhibitors of hydrogen peroxide and superoxide, which were produced by mitochondria under stress, could inhibit the phosphorylation of c-Jun in XIAP knockdown cells. In conclusion, it is the first time to show that both NF-kappaB and antioxidants can counteract TGF-beta1-induced apoptosis in hepatic cell death through JNK1 pathway.
Wang
Fang
F
Department of Pharmacology & Toxicology, Indiana University Purdue University Indianapolis, 1044 W. Walnut St., Indianapolis, IN 46224, USA. wang44@iupui.edu
Kaur
Swayamjot
S
Cavin
Lakita G
LG
Arsura
Marcello
M
D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D045744:Cell Line, Tumor; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism*; D048670:MAP Kinase Kinase 4 / Q000037:antagonists & inhibitors / Q000378:metabolism; D020930:MAP Kinase Kinase Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000235:genetics / Q000378:metabolism; D000099151:MAP Kinase Kinase Kinase 7
D000975:Antioxidants; D048670:MAP Kinase Kinase 4; D020930:MAP Kinase Kinase Kinases; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D053773:Transforming Growth Factor beta1; D051636:X-Linked Inhibitor of Apoptosis Protein; D000099151:MAP Kinase Kinase Kinase 7; C496866:XIAP protein, human