Baicalein modulates Nrf2/Keap1 system in both Keap1-dependent and Keap1-independent mechanisms

Si Qin, Fangming Deng, Weiguo Wu, Liwen Jiang, Takaaki Yamashiro, Satoshi Yano, De Xing Hou*

*この研究の対応する著者

研究成果: Article査読

29 被引用数 (Scopus)

抄録

Baicalein, a major component of Scutellaria baicalensis Georgi (Huang Qin), is widely used in the traditional Chinese medicine. However, the mechanisms underlying cancer chemoprevention are still not clear. The present study aimed to clarify how baicalein modulate Nrf2/Keap1 system to exert its cytoprotection and cancer chemoprevention. In the upstream cellular signaling, baicalein stimulated the phosphorylation of MEK1/2, AKT and JNK1/2, which were demonstrated to be essential for baicalein-induced Nrf2 expression by their inhibitors. Immunoprecipitation with Nrf2 found that baicalein increased the amount of phosphorylated MEK1/2, AKT and JNK1/2 bound to Nrf2, and also stabilized Nrf2 protein by inhibiting the ubiquitination and proteasomal turnover of Nrf2. Simultaneously, baicalein down-regulated Keap1 by stimulating modification and degradation of Keap1 without affecting the dissociation of Keap1-Nrf2. Silencing Nrf2 using Nrf2 siRNA markedly reduced the ARE activity under both baseline and baicalein-induced conditions. Thus, baicalein positively modulate Nrf2/Keap1 system through both Keap1-independent and -dependent pathways. These finding provide an insight to understand the mechanisms of baicalein in cytoprotection and cancer chemoprevention.

本文言語English
ページ(範囲)53-61
ページ数9
ジャーナルArchives of Biochemistry and Biophysics
559
DOI
出版ステータスPublished - 2014 10月 1
外部発表はい

ASJC Scopus subject areas

  • 生物理学
  • 生化学
  • 分子生物学

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