Regulation of GCL activity and cellular glutathione through inhibition of ERK phosphorylation

Zhi Hua Chen, Yoshiro Saito, Yasukazu Yoshida, Noriko Noguchi, Etsuo Niki

研究成果: Article査読

6 被引用数 (Scopus)

抄録

Extracellular signal-regulated protein kinase (ERK), one of the mitogen-activated protein kinase, has been known to be involved in diverse cellular functions. In this work, we found that basically inhibition of this kinase in cultured cells markedly increased the γ-glutamate-cysteine ligase (GCL; EC 6.3.2.2) activity, but without any considerable induction of the GCL genes. The increased GCL activity consequently elevated the cellular GSH level and eventually enhanced the cellular antioxidant capacity. Genetic inhibition of B-Raf, the upstream of ERK, also resulted in increased GCL activity and GSH level. Recent evidence also suggests that chronic pro-oxidant exposure results in the loss of ERK phosphorylation in vivo. Therefore, the findings in the present study suggest that inhibition of B-Raf/MEK/ERK pathway might be a promising physiological approach to up-regulate GCL activity and GSH. This study would also help us to understand the comprehensive role of the Raf/MEK/ERK pathway in overall physio/pathological conditions.

本文言語English
ページ(範囲)1-11
ページ数11
ジャーナルBioFactors
33
1
DOI
出版ステータスPublished - 2008
外部発表はい

ASJC Scopus subject areas

  • 生化学
  • 分子医療
  • 臨床生化学

フィンガープリント

「Regulation of GCL activity and cellular glutathione through inhibition of ERK phosphorylation」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル