Novel n-3 fatty acid oxidation products activate Nrf2 by destabilizing the association between Keap1 and Cullin3.

Novel n-3 fatty acid oxidation products activate Nrf2 by destabilizing the association between Keap1 and Cullin3. Research Abstract Details 

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Novel n-3 fatty acid oxidation products activate Nrf2 by destabilizing the association between Keap1 and Cullin3. Abstract Text:

Ling Gao,Jiakun Wang,Konjeti R Sekhar,Huiyong Yin,Nicholas F Yared,Scott N Schneider,Soumya Sasi,Timothy P Dalton,Mark E Anderson,Jefferson Y Chan,Jason D Morrow,Michael L Freeman,

Consumption of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) can mitigate the progression of diseases in which oxidative stress represents a common underlying biochemical process. Nrf2-regulated gene expression regulates detoxification of reactive oxygen species. EPA and DHA were subjected to an in vitro free radical oxidation process that models in vivo conditions. Oxidized n-3 fatty acids reacted directly with the negative regulator of Nrf2, Keap1, initiating Keap1 dissociation with Cullin3, thereby inducing Nrf2-directed gene expression. Liquid chromatography-tandem mass spectrometry analyses of oxidized EPA demonstrated the presence of novel cyclopentenone-containing molecules termed J3-isoprostanes in vitro and in vivo and were shown to induce Nrf2-directed gene expression. These experiments provide a biochemical basis for the hypothesis that formation of J-ring compounds generated from oxidation of EPA and DHA in vivo can reach concentrations high enough to induce Nrf2-based cellular defense systems.

Novel n-3 fatty acid oxidation products activate Nrf2 by destabilizing the association between Keap1 and Cullin3. Publishing Authors By Initials

L Gao,J Wang,KR Sekhar,H Yin,NF Yared,SN Schneider,S Sasi,TP Dalton,ME Anderson,JY Chan,JD Morrow,ML Freeman,

For similar genetic processes: gene expression regulation: trans-activation (genetics) research abstracts see: genetic processes: gene expression regulation: trans-activation (genetics) research

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Novel n-3 fatty acid oxidation products activate Nrf2 by destabilizing the association between Keap1 and Cullin3. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: The Journal of biological chemistry

VOLUME: 282

Page Numbers: 2529-37

Journal Abbreviation: J. Biol. Chem.

ISSN: 0021-9258

DAY: 25

MONTH: 11

YEAR: 2006

Novel n-3 fatty acid oxidation products activate Nrf2 by destabilizing the association between Keap1 and Cullin3. Information

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LANGUAGE: eng

NlmUniqueID: 2985121

Novel n-3 fatty acid oxidation products activate Nrf2 by destabilizing the association between Keap1 and Cullin3. Keywords Mesh Terms:

KEYWORDS: Trans-Activation (Genetics)

MESH TERMS: genetics

Chemical & Substance for Abstract: Novel n-3 fatty acid oxidation products activate Nrf2 by destabilizing the association between Keap1 and Cullin3. Information

Substance Name: NF-E2-Related Factor 2

Registry Number: 0

Grant and Affiliation Information for Novel n-3 fatty acid oxidation products activate Nrf2 by destabilizing the association between Keap1 and Cullin3.

AFFILIATION: Department of Medicine, Division of Clinical Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.

Country: United States

AGENCY: United States NCI

GRANT: T32 CA093240

ACRONYM: CA

MEDLINETA: J Biol Chem

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