Ascorbate antagonizes nickel ion to regulate JMJD1A expression in kidney cancer cells
| Autor: | Yaoting Gui, Xiang-lin Duan, Jingxiao Lu, Yuejia Wang, Zhiming Cai, Xiao-Qiang Guo |
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| Rok vydání: | 2012 |
| Předmět: |
Male
Jumonji Domain-Containing Histone Demethylases Blotting Western Biophysics Ascorbic Acid Kidney Biochemistry Antioxidants Mice Nickel Cell Line Tumor Animals Humans Regulation of gene expression Mice Inbred BALB C biology Dose-Response Relationship Drug Reverse Transcriptase Polymerase Chain Reaction Glucose transporter Kidney metabolism General Medicine Hypoxia-Inducible Factor 1 alpha Subunit Molecular biology Immunohistochemistry Kidney Neoplasms Gene Expression Regulation Neoplastic Vascular endothelial growth factor A HEK293 Cells Cell culture biology.protein Demethylase GLUT1 Hypoxia Pathway Drug Antagonism |
| Zdroj: | Acta biochimica et biophysica Sinica. 44(4) |
| ISSN: | 1745-7270 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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