Abstract
Cadmium (Cd) is a known environmental pollutant that can cause a variety of diseases and cancers. Glutathione (GSH) and metallothionein (MT) are the major factors to protect cells from Cd toxicity. Besides that, heme oxygenase (HO-1) is also involved in reducing the Cd-induced damaging effect. We investigated in this study the expression of MT, GSH and HO-1 under Cd exposure. Chinese hamster ovary (CHO K1) cells, an MT quiescent cell line, were treated with Cd and GSH content was examined. GSH increased with Cd treatment, and the increase was correlated with the activation of γ-glutamylcysteine synthetase (γ-GCS) expression after Cd stimulation. Overexpression of metal-responsive transcription factor 1 (MTF-1) or cellular myelocytomatosis oncogene (c-Myc) gene did not affect the γ-GCS level in Cd-treated cells. Similarly, knockdown of c-Myc gene expression did not alter γ-GCS level. Cd treatment elevated HO-1 levels in a dose- and time-dependent manner. However, HO-1 level was not affected by overexpression of either MTF-1 or c-Myc gene, or knockdown of c-Myc mRNA. Noticeably, HO-1 increased with the knockdown of MTF-1 expression. Analysis of the activity of c-jun NH2-terminal protein kinase (JNK) and c-Jun revealed that both increased with the increments of Cd concentration. Administration inhibitor for JNK or reactive oxygen species (ROS) resulted in a decreased HO-1 level and a decreased activity of JNK and c-Jun. A higher Cd concentration was required to stimulate JNK and c-Jun activity in MT gene highly amplified CHO cells (CdR) as compared to that of parental CHO K1 cells. On the contrary, knockdown of MTF-1 expression decrease MT expression but increased HO-1 level in Cd-treated CdR cells. Our results indicate that MT plays an effective role in reducing Cd toxicity. With the defect of MT gene expression, GSH and HO-1 are produced to attenuate Cd-induced toxicological effects.