Song Min Ok, Freedman Jonathan H
Nicholas School of the Environment and Earth Sciences, Duke University, Durham, North Carolina 27708-0328, USA.
Mol Cell Biochem. 2005 Nov;279(1-2):141-7. doi: 10.1007/s11010-005-8286-0.
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.
研究了铜调节细胞内信号转导通路活性以影响转录，最终破坏正常发育的假说。对暴露于铜4小时和24小时的HepG2细胞转录组进行的初步分析分别鉴定出19个和7个上调基因（两倍；p≤0.05）。在上调基因中，有几个先前已报道对金属或氧化应激有反应。基于基因本体论（GO），差异表达基因按功能类别分组。显著富集的GO类别（p<0.01）包括铜离子稳态、镉和铜离子结合以及血红素加氧酶和氧化还原酶活性。实时RT-PCR证实了铜对MT2A、HSPA1A、CYP1A1和HMOX1表达水平的影响。
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