JWA gene is involved in cadmium-induced growth inhibition and apoptosis in HEK-293T cells

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 mu M 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 (O-2(-.) 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.