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

Qunxiang Ong1, Shunling Guo, Kai Zhang

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

ACS Chemical Neuroscience
|December 30, 2014
PubMed

Insights

U0126, a MEK inhibitor, also acts as a direct antioxidant. This antioxidant function is independent of MEK inhibition and may affect previous research findings.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Pharmacology

Background:

  • U0126 is a widely used inhibitor of the Ras/Raf/MEK/ERK signaling pathway.
  • Previous studies utilized U0126 to demonstrate MEK pathway inhibition's neuroprotective effects against oxidative stress.

Purpose of the Study:

  • To investigate the antioxidant properties of U0126.
  • To determine if U0126's protective effects against oxidative stress are mediated by MEK inhibition.

Main Methods:

  • Testing U0126's protective effects against various oxidative-stress inducers in PC12 cells.
  • Comparing U0126's effects with other MEK inhibitors.
  • Assessing U0126's ability to scavenge reactive oxygen species (ROS) in vitro.
  • Analyzing the fluorescence of U0126 oxidation products.

Main Results:

  • U0126 protects PC12 cells from oxidative stress independently of MEK inhibition.
  • Other MEK inhibitors did not replicate U0126's protective effects.
  • U0126 directly scavenges ROS in vitro.
  • Oxidized U0126 exhibits fluorescence.

Conclusions:

  • U0126 possesses significant antioxidant activity.
  • The antioxidant function of U0126 is distinct from its role as a MEK inhibitor.
  • Caution is advised when using U0126 as a MEK inhibitor and when interpreting past research due to its antioxidant properties.
Keywords:
MEK inhibitorU0126antioxidantcell deathoxidative stress

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