Affiliations: Human Stress Signal Research Center (HSSRC), National
Institute of Advanced Industrial Science & Technology (AIST), Osaka,
Japan | Research Center for Advanced Science and Technology,
University of Tokyo, Tokyo, Japan | Science and Engineering Research Institute, Doshisha
University, Kyoto, Japan
Note: [] Address for correspondence: Dr. Yoshiro Saito, Human Stress
Signal Research Center (HSSRC), National Institute of Advanced Industrial
Science & Technology (AIST), 1-8-31, Midorigaoka, Ikeda, Osaka,
563-8577, Japan. E-mail: ysaito@mail.doshisha.ac.jp
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.
