論文

査読有り
2016年1月

Exendin-4 promotes extracellular-superoxide dismutase expression in A549 cells through DNA demethylation

JOURNAL OF CLINICAL BIOCHEMISTRY AND NUTRITION
  • Hiroyuki Yasuda
  • ,
  • Koji Mizukami
  • ,
  • Mutsuna Hayashi
  • ,
  • Tetsuro Kamiya
  • ,
  • Hirokazu Hara
  • ,
  • Tetsuo Adachi

58
1
開始ページ
34
終了ページ
39
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.3164/jcbn.15-16
出版者・発行元
JOURNAL CLINICAL BIOCHEMISTRY & NUTRITION

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.

Web of Science ® 被引用回数 : 8

リンク情報
DOI
https://doi.org/10.3164/jcbn.15-16
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/26798195
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000382274900006&DestApp=WOS_CPL