Nickel and cadmium-induced SLBP depletion: A potential pathway to metal mediated cellular transformation.
Nickel and cadmium-induced SLBP depletion: A potential pathway to metal mediated cellular transformation.
复制标题
DOI：
10.1371/journal.pone.0173624
复制
发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Costa M
中科院分区：
文献类型：
--
作者：
Jordan A;Zhang X;Li J;Laulicht-Glick F;Sun H;Costa M
几十年来，镍和镉化合物都被确定为I类致癌物质。尽管有令人印象深刻的证据表明这些化合物对人类具有致癌作用，但控制金属诱导细胞转化的具体潜在分子机制仍不清楚。在这项研究中，我们发现，在我们的镍暴露细胞中，SLBP mRNA和蛋白的降低以及Polya H3.1的升高的影响略有不同。这表明镍和砷对组蛋白基因转录和翻译有相似的影响。我们还看到，通过抑制蛋白小体，SLBP蛋白的耗竭被逆转。最后，我们发现抑制SLBP的mRNA和蛋白水平可以被表观遗传修饰物拯救，这表明镍对SLBP的影响可能是通过表观遗传机制来调节的。综上所述，这些结果表明，砷和镍可能发挥致癌作用的机制相似。
Both nickel and cadmium compounds have been established as group I carcinogens for several decades. Despite over-whelming evidence of these compounds’ carcinogenicity in humans, the specific underlying molecular mechanisms that govern metal induced cellular transformation remain unclear. In this study, we found that there were slightly different effects on decreased SLBP mRNA and protein as well as increased polyA H3.1 in our nickel exposed cells. This suggested that nickel and arsenic have similar effects on canonical histone mRNA transcription and translation. We also saw that the depletion of SLBP protein was reversed by inhibiting the proteosome. Finally, we showed that inhibiting the SLBP mRNA and protein levels were rescued by epigenetic modifiers suggesting that nickel’s effects on SLBP may be mediated via epigenetic mechanisms. Taken together these results suggest a similar mechanism by which both arsenic and nickel may exert their carcinogenic effects.