Effects of cadmium on GAPDH protein and NEMO gene expression relating to G-6-PD gene in HEPG2 cells

Abstract

Cadmium is an ubiquitous environmental contaminants in environmental medium, food and herbal medicines. Previous studies reported that cadmium decreased the activity of G-6-PD and GAPDH but the effect of cadmium to G-6-PD and GAPDH gene expression are not yet clearly understood. In this thesis, we found that G-6-PD mRNA expression was inhibited by cadmium. Moreover, GAPDH and LDHA proteins are concomitantly decreased after cadmium exposure. However it increased histone H2B truncation in HepG2 cells. These results are related to the mechanisms of cell necrosis because cadmium induced 55 kDa PARP-1 cleavage in a dose-response manner. In HepG2 cells, reduced GAPDH protein expression is recovered by insulin treatment. The alteration of redox system protein may assist in understand molecular mechanism of cadmium toxicity and the truncation of histone H2B may assist in cadmium induced cell death through epigenetic mechanisms. These results bright about to better the understanding in hepatocellular injury in relation to adaptive coping of cadmium toxicity.