U0126 protects cells against oxidative stress independent of its function as a MEK inhibitor

Qunxiang Ong, Shunling Guo, Kai Zhang, Bianxiao Cui

Research output: Contribution to journalArticlepeer-review

Abstract

U0126 is a potent and selective inhibitor of MEK1 and MEK2 kinases. It has been widely used as an inhibitor for the Ras/Raf/MEK/ERK signaling pathway with over 5000 references on the NCBI PubMed database. In particular, U0126 has been used in a number of studies to show that inhibition of the Raf/MEK/ERK pathway protects neuronal cells against oxidative stress. Here, we report that U0126 can function as an antioxidant that protects PC12 cells against a number of different oxidative-stress inducers. This protective effect of U0126 is independent of its function as a MEK inhibitor, as several other MEK inhibitors failed to show similar protective effects. U0126 reduces reactive oxygen species (ROS) in cells. We further demonstrate that U0126 is a direct ROS scavenger in vitro, and the oxidation products of U0126 exhibit fluorescence. Our finding that U0126 is a strong antioxidant signals caution for its future usage as a MEK inhibitor and for interpreting some previous results.

Original languageEnglish (US)
Pages (from-to)130-137
Number of pages8
JournalACS Chemical Neuroscience
Volume6
Issue number1
DOIs
StatePublished - Jan 21 2015

Keywords

  • MEK inhibitor
  • U0126
  • antioxidant
  • cell death
  • oxidative stress

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Cognitive Neuroscience
  • Cell Biology

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