Involvement of ROS and JNK1 in selenite-induced apoptosis in Chang liver cells.
Selenium is a dietary essential trace nutrient with important biological roles. Selenocompounds were reported to induce apoptosis in many types of tumor cells. In this study, we investigated the signaling pathway involved in the selenite-induced apoptosis using Chang liver cells as a non-malignant cell model. The Chang liver cell apoptosis induced by selenite (10 microM) was confirmed by DNA fragmentation and typical apoptotic nuclear changes. Treatment of selenite increased intracellular reactive oxygen species (ROS) level and c-Jun N-terminal kinase1 (JNK1) phosphorylation. The selenite-induced cell death was attenuated by SP600125, a specific inhibitor of JNK, and by dominant negative JNK1 (DN-JNK1). Antioxidants such as glutathione (GSH), N-acetyl cysteine (NAC), curcumin, epigallocatechin gallate (EGCG) and epicatechin (EC) inhibited selenite-induced intracellular ROS elevation and JNK1 phosphorylation. Our results suggest that selenite-induced apoptosis in Chang liver cells was preceded by the ROS generation and JNK1 activation.
Kim
Yong-sook
YS
Department of Food and Nutrition, College of Human Ecology Chonnam National University, Gwangju 500-757, Korea.
Jhon
Deok-young
DY
Lee
Kee-Young
KY
D000111:Acetylcysteine / Q000494:pharmacology; D000873:Anthracenes / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002460:Cell Line; D053938:DNA Fragmentation / Q000187:drug effects*; D016166:Free Radical Scavengers / Q000494:pharmacology; D006801:Humans; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D048055:Mitogen-Activated Protein Kinase 8 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012643:Selenium / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects
D000873:Anthracenes; D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; C432165:pyrazolanthrone; D002392:Catechin; C045651:epigallocatechin gallate; D048055:Mitogen-Activated Protein Kinase 8; D012643:Selenium; D000111:Acetylcysteine