Vitamin C is a kinase inhibitor: Dehydroascorbic acid inhibits IκBα kinase β Journal Article
| Authors: | Cárcamo, J. M.; Pedraza, A.; Borquez-Ojeda, O.; Zhang, B.; Sanchez, R.; Golde, D. W. |
| Article Title: | Vitamin C is a kinase inhibitor: Dehydroascorbic acid inhibits IκBα kinase β |
| 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 IκBα kinase β (IKKβ) and IKKα 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 IKKβ, NF-κB 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-κB signaling events. AA quenches ROS intermediates involved in the activation of NF-κB and is oxidized to DHA, which directly inhibits IKKβ and IKKα 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-κB signaling. |
| Keywords: | signal transduction; controlled study; unclassified drug; human cell; models, biological; oxygen; protein binding; down-regulation; immunoglobulin enhancer binding protein; dose-response relationship, drug; hela cells; transfection; dna; enzyme inhibitors; protein-serine-threonine kinases; enzyme inactivation; immunoblotting; reactive oxygen species; reactive oxygen metabolite; antioxidant; oxidative stress; antioxidants; ascorbic acid; adenosine triphosphate; luciferases; dehydroascorbic acid; phosphotransferase inhibitor; oxidation reduction reaction; i kappa b kinase; i-kappa b kinase; i kappa b alpha; humans; human; priority journal; article; i kappa b alpha kinase beta |
| Journal Title: | Molecular and Cellular Biology |
| Volume: | 24 |
| Issue: | 15 |
| ISSN: | 0270-7306 |
| Publisher: | American Society for Microbiology |
| Date Published: | 2004-08-01 |
| Start Page: | 6645 |
| End Page: | 6652 |
| Language: | English |
| DOI: | 10.1128/mcb.24.15.6645-6652.2004 |
| PROVIDER: | scopus |
| PMCID: | PMC444845 |
| PUBMED: | 15254232 |
| DOI/URL: | |
| Notes: | Mol. Cell. Biol. -- Cited By (since 1996):41 -- Export Date: 16 June 2014 -- CODEN: MCEBD -- Source: Scopus |
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