title: JWA gene is involved in cadmium-induced growth inhibition and apoptosis in HEK-293T cells.
abstract: Cadmium (Cd) is widely dispersed in the environment due to occupational and personal (cigarette) emissions. Exposure of human embryonic kidney 293T (HEK-293T) cells to CdCl2 resulted in growth inhibition and apoptosis. Our previous studies demonstrated that JWA, a novel retinoic acid-inducible and cytoskeleton-associated gene, is a potential environmental-responsive gene with increased expression attributed to oxidative and heat-shock stresses. In the present study, JWA was also found to be responsive to Cd exposure. After treatment with 20 microM CdCl2 for 12 h, the expression level of JWA was increased with accompanied growth inhibition and apoptosis. In addition, knock-down JWA protein expression by using transient transfecting of HEK-293T cells with antisense JWA express vector showed a protective effect against Cd-induced apoptosis. To determine whether the upregulation of JWA by Cd involved regulation by transcriptional mechanisms, further reporter gene assays were employed, which demonstrated a marked increase in JWA promoter activity. In addition, elevated intracellular levels of ROS components (O2-* and H2O2) and activation of JNK, ERK, and MAPK were found with corresponding upregulation of JWA protein expression. These results suggest that Cd-induced growth inhibition and apoptosis may involve ROS generation and subsequent affect on MAPK signal pathway. JWA responsiveness to CdCl2 might be through both transcriptional and posttranslational mechanisms.
authors.affiliation: Department of Molecular Cell Biology and Toxicology, School of Public Health, Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: Xing-Jiang
authors.initials: XJ
authors.lastname: Cao
authors.forename: Rui
authors.initials: R
authors.lastname: Chen
authors.forename: Ai-Ping
authors.initials: AP
authors.lastname: Li
authors.forename: Jian-Wei
authors.initials: JW
authors.lastname: Zhou
mesh_terms: D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D015153:Blotting, Western; D019256:Cadmium Chloride / Q000633:toxicity*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D016373:DNA, Antisense / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000633:toxicity*; D005562:Formazans / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects*; D020868:Gene Silencing; D006360:Heat-Shock Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D026901:Membrane Transport Proteins; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D013778:Tetrazolium Salts / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: C484566:ARL6IP5 protein, human; D016373:DNA, Antisense; D004785:Environmental Pollutants; D005562:Formazans; D006360:Heat-Shock Proteins; D047908:Intracellular Signaling Peptides and Proteins; D026901:Membrane Transport Proteins; D017382:Reactive Oxygen Species; D013778:Tetrazolium Salts; C079782:MTT formazan; D020929:Mitogen-Activated Protein Kinase Kinases; D019256:Cadmium Chloride