Antisense oligonucleotide of c-myc discriminates between zinc- and dexamethasone-induced synthesis of metallothionein.
Antisense oligonucleotide of c-myc discriminates between zinc- and dexamethasone-induced synthesis of metallothionein.
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c-myc 的反义寡核苷酸区分锌和地塞米松诱导的金属硫蛋白合成。
作者：
Takeda,A;Norris,JS;Iversen,PL;Ebadi,M
金属硫蛋白II基因由三个外显子和两个内含子组成，其结构在整个动物界高度保守。通过使用合成的寡核苷酸与编码人金属硫蛋白II的mRNA序列互补，我们已经表明：（a）金属硫蛋白合成的抑制导致细胞死于金属毒性，（B）金属硫蛋白具有必需基因，和（c）寡核苷酸结构的修饰在抑制金属硫蛋白合成中表现出特异性。此外，我们已经制备了一种合成的反义寡核苷酸的mRNA特异性的人c-myc和测试其潜力，调节金属硫蛋白在Chang肝细胞的合成培养。这项研究的结果表明，c-myc正义寡脱氧核苷酸导致更大的诱导锌促进，但不是镉或地塞米松诱导的金属硫蛋白的合成。这些数据被解释为表明，c-mycacts作为一个阻遏物的六个人类金属硫蛋白亚型中的至少一个，并展示了一个独特的模式，能够区分锌和地塞米松诱导的金属硫蛋白的合成的调节。
The metallothionem II genes, whose structures are highly conserved throughout the animal kingdom, are composed of three exons and two introns. By using synthetic oligonucleotides with sequences complementary to the mRNA coding for human metallothionem II, we have shown that (a) inhibition of metallothionem synthesis causes cells to die from metal toxicity, (b) metallothionem possesses an essential gene, and (c) modifications in oligonucleotide structures exhibit specificity in inhibiting metallothionem synthesis. Furthermore, we have prepared a synthetic antisense oligodeoxyribonucleotide to the mRNA specific for human c-mycand tested its potential to regulate metallothionein synthesis in Chang liver cells in culture. The results of this study revealed that the c-mycantisense oligodeoxyribonucleotide led to greater induction of zinc-promoted but not of cadmium- or dexamethasone-induced synthesis of metallothionein. These data are interpreted to suggest that c-mycacts as a repressor of at least one of the six human metallothionein isoforms and demonstrates a unique mode of regulation capable of discriminating between zinc- and dexamethasone-induced synthesis of metallothionein.