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标题：Exendin-4 promotes extracellular-superoxide dismutase expression in A549 cells through DNA demethylation
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作者：Hiroyuki Yasuda ; Koji Mizukami ; Mutsuna Hayashi 等
期刊名称：Journal of Clinical Biochemistry and Nutrition
印刷版ISSN：0912-0009
电子版ISSN：1880-5086
出版年度：2016
卷号：58
期号：1
页码：34-39
DOI：10.3164/jcbn.15-16
出版社：The Society for Free Radical Research Japan
摘要：Exendin-4 is an agonist of the glucagon-like peptide 1 receptor (GLP-1R) and is used in the treatment of type 2 diabetes. Since human GLP-1R has been identified in various cells besides pancreatic cells, exendin-4 is expected to exert extrapancreatic actions. It has also been suggested to affect gene expression through epigenetic regulation, such as DNA methylation and/or histone modifications. Furthermore, the expression of extracellular-superoxide dismutase (EC-SOD), a major SOD isozyme that is crucially involved in redox homeostasis, is regulated by epigenetic factors. In the present study, we demonstrated that exendin-4 induced the demethylation of DNA in A549 cells, which, in turn, affected the expression of EC-SOD. Our results showed that the treatment with exendin-4 up-regulated the expression of EC-SOD through GLP-1R and demethylated some methyl-CpG sites (methylated cytosine at 5'-CG-3') in the EC-SOD gene. Moreover, the treatment with exendin-4 inactivated DNA methyltransferases (DNMTs), but did not change their expression levels. In conclusion, the results of the present study demonstrated for the first time that exendin-4 regulated the expression of EC-SOD by reducing the activity of DNMTs and demethylation of DNA within the EC-SOD promoter region in A549 cells.
关键词：exendin-4;extracellular-superoxide dismutase;epigenetics;DNA demethylation