Vitamin C is a kinase inhibitor: dehydroascorbic acid inhibits IkappaBalpha kinase beta

  • Carcamo J
  • Pedraza A
  • Borquez-Ojeda O
 et al. 
  • 3

    Readers

    Mendeley users who have this article in their library.
  • N/A

    Citations

    Citations of this article.

Abstract

Reactive oxygen species (ROS) are key intermediates in cellular signal transduction pathways whose function may be counterbalanced by antioxidants. Acting as an antioxidant, ascorbic acid (AA) donates two electrons and becomes oxidized to dehydroascorbic acid (DHA). We discovered that DHA directly inhibits IkappaBalpha kinase beta (IKKbeta) and IKKalpha enzymatic activity in vitro, whereas AA did not have this effect. When cells were loaded with AA and induced to generate DHA by oxidative stress in cells expressing a constitutive active IKKbeta, NF-kappaB activation was inhibited. Our results identify a dual molecular action of vitamin C in signal transduction and provide a direct linkage between the redox state of vitamin C and NF-kappaB signaling events. AA quenches ROS intermediates involved in the activation of NF-kappaB and is oxidized to DHA, which directly inhibits IKKbeta and IKKalpha enzymatic activity. These findings define a function for vitamin C in signal transduction other than as an antioxidant and mechanistically illuminate how vitamin C down-modulates NF-kappaB signaling.

Author-supplied keywords

  • Adenosine Triphosphate/metabolism
  • Antioxidants/metabolism
  • Ascorbic Acid/metabolism/*pharmacology
  • DNA/metabolism
  • Dehydroascorbic Acid/*pharmacology
  • Dose-Response Relationship, Drug
  • Down-Regulation
  • Enzyme Inhibitors/*pharmacology
  • Hela Cells
  • Human
  • Immunoblotting
  • Luciferase/metabolism
  • Models, Biological
  • Oxidative Stress
  • Oxygen/metabolism
  • Protein Binding
  • Protein-Serine-Threonine Kinases/*antagonists & in
  • Reactive Oxygen Species
  • Signal Transduction
  • Support, Non-U.S. Gov't
  • Support, U.S. Gov't, P.H.S.
  • Transfection

Get free article suggestions today

Mendeley saves you time finding and organizing research

Sign up here
Already have an account ?Sign in

Authors

  • J M Carcamo

  • A Pedraza

  • O Borquez-Ojeda

  • B Zhang

  • R Sanchez

  • D W Golde

Cite this document

Choose a citation style from the tabs below

Save time finding and organizing research with Mendeley

Sign up for free