Open AccessVitamin C Is a Kinase Inhibitor: Dehydroascorbic Acid Inhibits IκBα Kinase β
Author(s) -
Juan M. Cárcamo,
Alicia Pedraza,
Oriana Bórquez-Ojeda,
Bing Zhang,
Roberto Sánchez,
David W. Golde
Publication year - 2004
Publication title -
molecular and cellular biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.14
H-Index - 327
eISSN - 1067-8824
pISSN - 0270-7306
DOI - 10.1128/mcb.24.15.6645-6652.2004
Subject(s) - dehydroascorbic acid , iκb kinase , ascorbic acid , signal transduction , biology , kinase , biochemistry , antioxidant , vitamin c , protein kinase c , reactive oxygen species , nf κb , microbiology and biotechnology , food science
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.