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 <or= 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.
Song
Min Ok
MO
Nicholas School of the Environment and Earth Sciences, Duke University, Durham, North Carolina 27708-0328, USA.
Freedman
Jonathan H
JH
D006528:Carcinoma, Hepatocellular; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003300:Copper / Q000633:toxicity*; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects*; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D015854:Up-Regulation
D018840:HSP70 Heat-Shock Proteins; C490786:HSPA1A protein, human; D012333:RNA, Messenger; D003300:Copper; D019363:Cytochrome P-450 CYP1A1; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1