Expression of copper-responsive genes in HepG2 cells

The hypothesis that copper modulates the activity of intracellular signal transduction pathways to affect transcription, which ultimately disrupts normal development was investigated. Preliminary analysis of transcriptomes from HepG2 cells exposed to copper for 4 and 24 h identified 19 and 7 up-regulated genes (twofold; p <= 0.05), respectively. Among the up-regulated genes, several have been previously reported to be responsive to metals or oxidative stress. Differentially expressed genes were grouped by the functional categories based on gene ontology (GO). Significantly enriched GO categories (p < 0.01) included copper ion homeostasis, cadmium and copper ion binding, and heme oxygenase and oxidoreductase activities. Real-time RT-PCR confirmed the effect of copper on the levels of MT2A, HSPA1A, CYP1A1 and HMOX1 expression.