Iron- and 2-oxoglutarate-dependent dioxygenases: an emerging group of molecular targets for nickel toxicity and carcinogenicity.
Iron- and 2-oxoglutarate-dependent dioxygenases: an emerging group of molecular targets for nickel toxicity and carcinogenicity.
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DOI：
10.1007/s10534-008-9190-3
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发表时间：
2009-02
期刊：
影响因子：
3.5
通讯作者：
Costa, Max
中科院分区：
文献类型：
--
作者：
Chen, Haobin;Costa, Max
镍化合物是重要的职业和环境污染物。长期接触这些污染物与呼吸道癌症和心血管疾病的风险增加有关。然而，目前还不清楚镍毒性和致癌性的具体分子靶点是什么。在这里，我们建议铁和2-酮戊二酸依赖性双加氧酶家族的酶是重要的细胞内目标，介导的毒性和致癌性的镍。为了支持这一假设，我们的数据表明，在这个铁和2-酮戊二酸依赖性双加氧酶家族，包括HIF-脯氨酰羟化酶PHD 2，组蛋白脱甲基酶JHDM 2A/JMJD 1A，和DNA修复酶ABH 3，三种不同类型的酶都是高度敏感的镍抑制。这些酶的失活解释了镍在细胞中引起的许多有害作用，即低氧模拟应激和异常表观遗传变化。镍对这些铁和2-酮戊二酸依赖性双加氧酶的影响的未来研究将加深我们对镍毒性和致癌性的理解。
Nickel compounds are important occupational and environmental pollutants. Chronic exposure to these pollutants has been connected with increased risks of respiratory cancers and cardiovascular diseases. However, it is still not clear what are the specific molecular targets for nickel toxicity and carcinogenicity. Here, we propose that the iron- and 2-oxoglutarate-dependent dioxygenase family enzymes are important intracellular targets that mediate the toxicity and carcinogenicity of nickel. In support of this hypothesis, our data show that three different classes of enzymes in this iron- and 2-oxoglutarate-dependent dioxygenase family, including HIF-prolyl hydroxylase PHD2, histone demethylase JHDM2A/JMJD1A, and DNA repair enzyme ABH3, are all highly sensitive to nickel inhibition. Inactivation of these enzymes accounts for a number of deleterious effects caused by nickel in cells, namely hypoxia-mimic stress and aberrant epigenetic changes. Future studies on nickel’s effects on these iron- and 2-oxoglutarate-dependent dioxygenases would deepen our understanding on nickel toxicity and carcinogenicity.
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影响因子：
64.5
作者：
Chen, Zhongzhou;Zang, Jianye;Zhang, Gongyi
通讯作者：
Zhang, Gongyi
影响因子：
3.8
作者：
Chen, HB;Davidson, T;Costa, M
通讯作者：
Costa, M
影响因子：
4.8
作者：
Salnikow, K;Donald, SP;Kasprzak, KS
通讯作者：
Kasprzak, KS
影响因子：
4.6
作者：
Davidson, Todd L.;Chen, Haobin;Costa, Max
通讯作者：
Costa, Max
DOI：
10.1080/00039896.1981.10667630
发表时间：
1981-01-01
期刊：
ARCHIVES OF ENVIRONMENTAL HEALTH
影响因子：
--
作者：
POLEDNAK, AP
通讯作者：
POLEDNAK, AP