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镉及其表观遗传效应。

Cadmium and its epigenetic effects.

机构信息

Department of Pathophysiology, Prostate Diseases Prevention and Treatment Research Center, Norman Bethune College of Medicine, Jilin University, Changchun, China.

出版信息

Curr Med Chem. 2012;19(16):2611-20. doi: 10.2174/092986712800492913.

Abstract

Cadmium (Cd) is a toxic, nonessential transition metal and contributes a health risk to humans, including various cancers and cardiovascular diseases; however, underlying molecular mechanisms remain largely unknown. Cells transmit information to the next generation via two distinct ways: genetic and epigenetic. Chemical modifications to DNA or histone that alters the structure of chromatin without change of DNA nucleotide sequence are known as epigenetics. These heritable epigenetic changes include DNA methylation, post-translational modifications of histone tails (acetylation, methylation, phosphorylation, etc), and higher order packaging of DNA around nucleosomes. Apart from DNA methyltransferases, histone modification enzymes such as histone acetyltransferase, histone deacetylase, and methyltransferase, and microRNAs (miRNAs) all involve in these epigenetic changes. Recent studies indicate that Cd is able to induce various epigenetic changes in plant and mammalian cells in vitro and in vivo. Since aberrant epigenetics plays a critical role in the development of various cancers and chronic diseases, Cd may cause the above-mentioned pathogenic risks via epigenetic mechanisms. Here we review the in vitro and in vivo evidence of epigenetic effects of Cd. The available findings indicate that epigenetics occurred in association with Cd induction of malignant transformation of cells and pathological proliferation of tissues, suggesting that epigenetic effects may play a role in Cd toxic, particularly carcinogenic effects. The future of environmental epigenomic research on Cd should include the role of epigenetics in determining long-term and late-onset health effects following Cd exposure.

摘要

镉(Cd)是一种有毒的、非必需的过渡金属,会给人类健康带来风险,包括各种癌症和心血管疾病;然而,其潜在的分子机制在很大程度上仍不清楚。细胞通过两种不同的方式将信息传递给下一代:遗传和表观遗传。DNA 或组蛋白的化学修饰改变了染色质的结构,而不改变 DNA 核苷酸序列,这种修饰被称为表观遗传。这些可遗传的表观遗传变化包括 DNA 甲基化、组蛋白尾部的翻译后修饰(乙酰化、甲基化、磷酸化等)以及核小体周围 DNA 的高级包装。除了 DNA 甲基转移酶外,组蛋白修饰酶如组蛋白乙酰转移酶、组蛋白去乙酰化酶和甲基转移酶,以及 microRNAs(miRNAs)都参与了这些表观遗传变化。最近的研究表明,Cd 能够在体外和体内诱导植物和哺乳动物细胞发生各种表观遗传变化。由于异常的表观遗传学在各种癌症和慢性疾病的发展中起着关键作用,因此 Cd 可能通过表观遗传机制引起上述致病风险。在这里,我们综述了 Cd 的体外和体内表观遗传效应的证据。现有研究结果表明,表观遗传学与 Cd 诱导的细胞恶性转化和组织病理性增殖有关,这表明表观遗传效应可能在 Cd 的毒性,特别是致癌效应中发挥作用。未来 Cd 的环境表观基因组学研究应包括表观遗传学在确定 Cd 暴露后长期和迟发性健康影响中的作用。

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