We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Regulation of GCL activity and cellular glutathione through inhibition of ERK phosphorylation.
- Authors
Chen, Zhi-Hua; Saito, Yoshiro; Yoshida, Yasukazu; Noguchi, Noriko; Niki, Etsuo
- 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.
- Subjects
PROTEIN kinases; MITOGEN-activated protein kinases; CELLS; GENES; ANTIOXIDANTS; PHOSPHORYLATION
- Publication
Biofactors, 2008, Vol 33, Issue 1, p1
- ISSN
0951-6433
- Publication type
Article
- DOI
10.1002/biof.5520330101