Ascorbate antagonizes nickel ion to regulate JMJD1A expression in kidney cancer cells

作者:Guo, Xiaoqiang; Lu, Jingxiao; Wang, Yuejia; Gui, Yaoting; Duan, Xianglin*; Cai, Zhiming
来源:Acta Biochimica et Biophysica Sinica, 2012, 44(4): 330-338.
DOI:10.1093/abbs/gms004

摘要

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.