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

Acta biochimica et biophysica Sinica (2012-02-10)
Xiaoqiang Guo, Jingxiao Lu, Yuejia Wang, Yaoting Gui, Xianglin Duan, Zhiming Cai
ABSTRACT

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-1α (HIF-1α). 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 NiCl(2) (2.5-100 μM) for 24 h, and found that JMJD1A mRNA and protein were up-regulated with increased concentrations of NiCl(2). We then observed that ascorbate could retard the up-regulated effect of NiCl(2)-induced JMJD1A expression in a dose-dependent manner through decreasing the stability of HIF-1α 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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Nickel(II) chloride, 98%
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Nickel(II) chloride hexahydrate, ReagentPlus®
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Nickel(II) chloride hexahydrate, BioReagent, suitable for cell culture
Sigma-Aldrich
Nickel(II) chloride, anhydrous, powder, 99.99% trace metals basis
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Nickel(II) chloride hexahydrate, puriss. p.a., ≥98%
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Nickel(II) chloride hexahydrate, 99.999% trace metals basis
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Nickel(II) chloride hydrate, 99.95% trace metals basis