Andrews G K, Adamson E D
Nucleic Acids Res. 1987 Jul 10;15(13):5461-75. doi: 10.1093/nar/15.13.5461.
The expression of metallothionein genes (MT-I and MT-II) was shown to be enhanced within 2 h of addition of 2.5-5 mM sodium butyrate to cultures of teratocarcinoma cells. Both undifferentiated stem cells (F9 and OC15) and differentiated cells (PSA5E and OC15 END) reacted similarly to butyrate by increased accumulation of MT mRNAs. As expected, all of the teratocarcinoma cells that were tested also responded to Zn2+ and Cd2+ by 5- to 10-fold increases in MT mRNA accumulation within 2-24 h of metal addition to the culture media. Surprisingly, MT genes in cells pretreated with butyrate were hypersensitive to metal induction, and this was demonstrated by accumulated transcript levels and by synthesis of MT protein. The maximal metal response was obtained by exposure of cells to butyrate for around 5-8 h together with 10 microM heavy metals. Metal additions to culture media over a range of concentrations and times only induced half the levels of MT mRNA that were achieved by butyrate plus metals. Butyrate enhanced the rate of accumulation of MT mRNA in response to metals, increased the sensitivity of the MT gene to metals, and protected cells from toxic effects of high concentrations of metals. The butyrate and metal ion responses were selective in that no accumulation of c-myc, c-fms, HSP-70, or AFP mRNA was detected. However, c-fos mRNA accumulated in cells exposed to toxic concentrations of metals (50 microM and higher) and this was also potentiated by butyrate treatment. These results suggest that butyrate alters the chromatin conformation of both the MT-I and MT-II genes leading to an accentuated transcriptional response to metals.
研究表明，在向畸胎瘤细胞培养物中添加2.5 - 5 mM丁酸钠后的2小时内，金属硫蛋白基因（MT - I和MT - II）的表达增强。未分化的干细胞（F9和OC15）以及分化细胞（PSA5E和OC15 END）对丁酸钠的反应相似，MT mRNA的积累均增加。正如预期的那样，所有测试的畸胎瘤细胞在向培养基中添加金属后的2 - 24小时内，MT mRNA的积累也因Zn2 +和Cd2 +而增加了5至10倍。令人惊讶的是，用丁酸钠预处理的细胞中的MT基因对金属诱导高度敏感，这通过积累的转录水平和MT蛋白的合成得以证明。通过将细胞暴露于丁酸钠约5 - 8小时并同时加入10 microM重金属，可获得最大的金属反应。在一系列浓度和时间范围内向培养基中添加金属，仅诱导出丁酸钠加金属所达到的MT mRNA水平的一半。丁酸钠提高了MT mRNA对金属的积累速率，增加了MT基因对金属的敏感性，并保护细胞免受高浓度金属的毒性作用。丁酸钠和金属离子的反应具有选择性，因为未检测到c - myc、c - fms、HSP - �0或AFP mRNA的积累。然而，c - fos mRNA在暴露于有毒浓度金属（50 microM及更高）的细胞中积累，并且丁酸钠处理也增强了这种积累。这些结果表明，丁酸钠改变了MT - I和MT - II基因的染色质构象，导致对金属的转录反应增强。
