1. Academic Validation
  2. U0126 protects cells against oxidative stress independent of its function as a MEK inhibitor

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

  • ACS Chem Neurosci. 2015 Jan 21;6(1):130-7. doi: 10.1021/cn500288n.
Qunxiang Ong 1 Shunling Guo Kai Zhang Bianxiao Cui
Affiliations

Affiliation

  • 1 Department of Chemistry, Stanford University , 380 Roth Way, Palo Alto, California 94305, United States.
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.

Keywords

MEK inhibitor; U0126; antioxidant; cell death; oxidative stress.

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