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Regulation of GCL activity and cellular glutathione through inhibition of ERK phosphorylation
Author(s) -
Chen ZhiHua,
Saito Yoshiro,
Yoshida Yasukazu,
Niki Etsuo,
Noguchi Noriko
Publication year - 2008
Publication title -
biofactors
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.204
H-Index - 94
eISSN - 1872-8081
pISSN - 0951-6433
DOI - 10.1002/biof.5520330101
Subject(s) - mapk/erk pathway , glutathione , microbiology and biotechnology , kinase , protein kinase a , phosphorylation , chemistry , signal transduction , extracellular , biochemistry , biology , enzyme
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.