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  • Title: JWA gene is involved in cadmium-induced growth inhibition and apoptosis in HEK-293T cells.
    Author: Cao XJ, Chen R, Li AP, Zhou JW.
    Journal: J Toxicol Environ Health A; 2007 Jun; 70(11):931-7. PubMed ID: 17479408.
    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.
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