Oxidative stress of CeO2 nanoparticles via p38-Nrf-2 signaling pathway in human bronchial epithelial cell, Beas-2B.
To understand the molecular mechanism of previously observed cerium oxide (CeO(2)) nanoparticles-induced oxidative stress, an in vitro toxicity assay was conducted using human bronchial epithelial cell, Beas-2B, focusing on the involvement of the oxidative stress responding signal transduction pathway and transcription factors in the toxicity of CeO(2) nanoparticles. Extracellular signal-regulating kinase (ERK), p38 and c-Jun N-terminal kinase (JNK) signaling pathways, along with nuclear factor-kappaB (NF-kappaB) and nuclear factor-E2-related factor-2 (Nrf-2), were investigated as the upstream events of oxidative stress from exposure to CeO(2) nanoparticles. The overall results suggest that CeO(2) nanoparticles may exert their toxicity through oxidative stress, as they cause significant increases in the cellular reactive oxygen species (ROS) concentrations, subsequently leading to the strong induction of heme oxygenase-1 (HO-1) via the p38-Nrf-2 signaling pathway. Further studies on the mechanism by which CeO(2) nanoparticles induce the p38-Nrf-2 signaling pathway are warranted for a better understanding of the CeO(2) nanoparticles-induced oxidative stress; studies with other signaling pathways, with concentration-response and time course experiments would also be justified.
Faculty of Environmental Engineering, College of Urban Science, University of Seoul, 90 Jeonnong-dong, Dongdaemun-gu, Seoul 130-743, Republic of Korea.
Hyun-Jeong
HJ
Eom
Jinhee
J
Choi
D015153:Blotting, Western; D001980:Bronchi / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002460:Cell Line; D002563:Cerium / Q000737:chemistry / Q000633:toxicity*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005434:Flow Cytometry; D051547:Heme Oxygenase-1 / Q000378:metabolism; D006801:Humans; D008027:Light; D020935:MAP Kinase Signaling System / Q000187:drug effects; D046529:Microscopy, Electron, Transmission; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D053758:Nanoparticles / Q000737:chemistry / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D010316:Particle Size; D012542:Scattering, Radiation; D013482:Superoxide Dismutase / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D051267:NF-E2-Related Factor 2; D002563:Cerium; C030583:ceric oxide; D051547:Heme Oxygenase-1; D013482:Superoxide Dismutase; D048051:p38 Mitogen-Activated Protein Kinases