title: MWCNTs Induce ROS Generation, ERK Phosphorylation, and SOD-2 Expression in Human Mesothelial Cells.
abstract: Biological oxidative responses are involved in the toxicity of multiwall carbon nanotubes (MWCNTs), which may cause asbestos-like pathogenicity. Superoxide dismutase 2 (SOD-2) has been proposed as a biomarker of early responses to mesothelioma-inducing fibers. This study was conducted to investigate the alteration of SOD-2 expression in the human mesothelial cell lines Met-5A after exposure to nontoxic doses of MWCNTs and the potential signaling pathway. The parameters measured included the viability, morphological change, superoxide formation, extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation, and messenger RNA (mRNA)/protein levels of SOD-2. Our results showed that MWCNTs upregulated SOD-2 expression at both mRNA and protein level. Coincidently, both superoxide formation and ERK1/2 phosphorylation were observed in Met-5A cells exposed to MWCNTs and were diminished by pretreatment with the reactive oxidative species (ROS) scavenger, N-acetyl-l-(+)-cysteine (NAC). To further investigate the role of ROS/ERK1/2 in MWCNTs-induced SOD-2 overexpression, prior to MWCNTs exposure, cells were pretreated with the Mitogen-activated protein kinase kinase 1/2 (MEK 1/2) inhibitor (U0126) or with NAC. Both pretreatments decreased the MWCNTs-induced overexpression of SOD-2. These results suggest that upregulation of SOD-2 in Met-5A cells exposed to MWCNTs is mediated by ROS formation and ERK1/2 activation.
authors.affiliation: Department of Occupational Diseases, Zhejiang Academy of Medical Sciences, Zhejiang, P. R. China.
authors.forename: Min
authors.initials: M
authors.lastname: Yu
authors.affiliation: Department of Hygiene, Zhejiang Academy of Medical Sciences, Zhejiang, P. R. China.
authors.forename: Riping
authors.initials: R
authors.lastname: Chen
authors.affiliation: Department of Occupational Diseases, Zhejiang Academy of Medical Sciences, Zhejiang, P. R. China.
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Jia
authors.affiliation: Department of Occupational Diseases, Zhejiang Academy of Medical Sciences, Zhejiang, P. R. China.
authors.forename: Junqiang
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Occupational Diseases, Zhejiang Academy of Medical Sciences, Zhejiang, P. R. China.
authors.forename: Jianlin
authors.initials: J
authors.lastname: Lou
authors.affiliation: Key Laboratory of Occupational Safety and Health, Beijing Municipal Institute of Labor Protection, Beijing, P. R. China.
authors.forename: Shichuan
authors.initials: S
authors.lastname: Tang
authors.affiliation: Department of Occupational Diseases, Zhejiang Academy of Medical Sciences, Zhejiang, P. R. China xingtyou@mail.hz.zj.cn.
authors.forename: Xing
authors.initials: X
authors.lastname: Zhang
mesh_terms: D002461:Cell Line, Transformed; D004848:Epithelium / Q000201:enzymology / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006801:Humans; D046529:Microscopy, Electron, Transmission; D037742:Nanotubes, Carbon; D010766:Phosphorylation; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism*; D000099156:Superoxide Dismutase 2
chemical_list: D048049:Extracellular Signal-Regulated MAP Kinases; D037742:Nanotubes, Carbon; D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase; D000099156:Superoxide Dismutase 2
keywords: extracellular signal-regulated kinase 1/2 phosphorylation; multiwall carbon nanotubes; reactive oxygen species; superoxide dismutase 2