Ascorbate antagonizes nickel ion to regulate JMJD1A expression in kidney cancer cells
Ascorbate antagonizes nickel ion to regulate JMJD1A expression in kidney cancer cells
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DOI：
10.1093/abbs/gms004
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发表时间：
2012-04-01
影响因子：
3.7
通讯作者：
Cai, Zhiming
中科院分区：
文献类型：
--
作者：
Guo, Xiaoqiang;Lu, Jingxiao;Cai, Zhiming
组蛋白去甲基化酶Jumonji结构域蛋白1A（JMJD 1A）的异常表达与多种肿瘤相关。JMJD 1A也是一个低氧反应基因，其表达受低氧诱导因子-1（HIF-1）的调控。在本研究中，我们确定了JMJD 1A在发育和缺氧通路中的作用。我们还检测了JMJD 1A和两个缺氧因子葡萄糖转运蛋白1（GLUT 1）和血管内皮生长因子（VEGF）在786-0和HEK 293细胞与不同浓度的NiCl 2（2.5 × 100 M）处理24 h后的表达，发现JMJD 1A mRNA和蛋白随NiCl 2浓度的增加而上调。我们观察到抗坏血酸通过降低HIF-1蛋白的稳定性，以剂量依赖的方式延缓NiCl 2诱导的JMJD 1A表达的上调效应。免疫组化分析进一步证实抗坏血酸拮抗Ni-2诱导的786-0、HEK 293和OS-RC-2细胞中JMJD 1A表达的上调。这些发现表明，Ni-2和抗坏血酸都可以调节组蛋白去甲基化酶JMJD 1A的表达，这对癌症的发展或抑制很重要。
Abnormal expression of histone demethylase Jumonji domain-containing protein 1A (JMJD1A) is associated with many kinds of cancers. JMJD1A is also a hypoxic response gene and its expression is regulated by hypoxia-inducible factor-1 (HIF-1). In this study, we determined the role of JMJD1A in development and hypoxia pathway. We also measured the expression of JMJD1A and two hypoxia factors glucose transporter 1 (GLUT1) and vascular endothelial growth factor (VEGF) in 786-0 and HEK293 cells treated with different concentrations of NiCl2 (2.5100 M) for 24 h, and found that JMJD1A mRNA and protein were up-regulated with increased concentrations of NiCl2. We then observed that ascorbate could retard the up-regulated effect of NiCl2-induced JMJD1A expression in a dose-dependent manner through decreasing the stability of HIF-1 protein. Immunohistochemical analysis further demonstrated ascorbate antagonized Ni-2-induced up-regulation of JMJD1A expression in 786-0, HEK293, and OS-RC-2 cells. These findings suggest that both Ni-2 and ascorbate can regulate the expression of histone demethylase JMJD1A, which is important for cancer development or inhibition.