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

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

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1-11
Number of pages11
JournalBioFactors
Volume33
Issue number1
DOIs
Publication statusPublished - 2008 Dec 1
Externally publishedYes

Keywords

  • B-Raf/MEK/ ERK
  • GCL
  • GSH
  • Oxidative stress
  • Phosphorylation/dephosphorylation

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Clinical Biochemistry

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