論文

査読有り
2013年8月

Epigenetic regulation of extracellular-superoxide dismutase in human monocytes

FREE RADICAL BIOLOGY AND MEDICINE
  • Tetsuro Kamiya
  • ,
  • Masatomo Machiura
  • ,
  • Junya Makino
  • ,
  • Hirokazu Hara
  • ,
  • Isao Hozumi
  • ,
  • Tetsuo Adachi

61
開始ページ
197
終了ページ
205
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1016/j.freeradbiomed.2013.04.013
出版者・発行元
ELSEVIER SCIENCE INC

Extracellular-superoxide dismutase (EC-SOD) is a major SOD isozyme mainly present in the vascular wall and plays an important role in normal redox homeostasis. We previously showed the significant reduction or induction of EC-SOD during human monocytic U937 or THP-1 cell differentiation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA), respectively; however, its cell-specific expression and regulation have not been fully elucidated. It has been reported that epigenetic factors, such as DNA methylation and histone modification, are involved in several kinds of gene regulation. In this study, we investigated the involvement of epigenetic factors in EC-SOD expression and determined high levels of DNA methylation within promoter and coding regions of EC-SOD in THP-1 cells compared to those in U937 cells. Moreover, treatment with a DNA methyltransferase inhibitor, 5-azacytidine, significantly induced the expression of EC-SOD in THP-1 cells, indicating the importance of DNA methylation in the suppression of EC-SOD expression; however, the DNA methylation status did not change during THP-1 cell differentiation induced by TPA. On the other hand, we detected histone H3 and H4 acetylation during differentiation. Further, pretreatment with histone acetyltransferase inhibitors, CPTH2 or garcinol, significantly suppressed the TPA-inducible EC-SOD expression. We also determined the epigenetic suppression of EC-SOD in peripheral blood mononuclear cells. Treatment with granulocyte macrophage colony-stimulating factor (GM-CSF)/granulocyte-CSF induced that expression. Overall, these findings provide novel evidence that cell-specific and TPA-inducible EC-SOD expression are regulated by DNA methylation and histone H3 and H4 acetylation in human monocytic cells. (C) 2013 Elsevier Inc. All rights reserved.

Web of Science ® 被引用回数 : 23

リンク情報
DOI
https://doi.org/10.1016/j.freeradbiomed.2013.04.013
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/23602908
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000320687300020&DestApp=WOS_CPL