Cellular redox signalling is mediated by the post-translational modification of proteins by reactive oxygen/nitrogen species or the products derived from their reactions. In the case of oxidized lipids, several receptor-dependent and -independent mechanisms are now emerging. At low concentrations, adaptation to oxidative stress in the vasculature appears to be mediated by induction of antioxidant defences, including the synthesis of the intracellular antioxidant glutathione. At high concentrations apoptosis occurs through mechanisms that have yet to be defined in detail. Recent studies have revealed a mechanism through which electrophilic lipids, formed as the reaction products of oxidation, orchestrate these adaptive responses in the vasculature. Using a proteomics approach, we have identified a subset of proteins in cells that we term the electrophile-responsive proteome. Electrophilic modification of thiol groups in these proteins can initiate cell signalling events through the transcriptional activation of genes regulated by consensus sequences for the antioxidant response element found in their promoter regions. The insights gained from our understanding of the biology of these mechanisms will be discussed in the context of cardiovascular disease.
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Conference Article|
February 01 2004
Mechanisms of signal transduction mediated by oxidized lipids: the role of the electrophile-responsive proteome
E.K. Ceaser;
E.K. Ceaser
Department of Pathology, Center for Free Radical Biology, University of Alabama at Birmingham, AL 35294-2180, U.S.A.
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D.R. Moellering;
D.R. Moellering
Department of Pathology, Center for Free Radical Biology, University of Alabama at Birmingham, AL 35294-2180, U.S.A.
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S. Shiva;
S. Shiva
Department of Pathology, Center for Free Radical Biology, University of Alabama at Birmingham, AL 35294-2180, U.S.A.
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A. Ramachandran;
A. Ramachandran
Department of Pathology, Center for Free Radical Biology, University of Alabama at Birmingham, AL 35294-2180, U.S.A.
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A. Landar;
A. Landar
Department of Pathology, Center for Free Radical Biology, University of Alabama at Birmingham, AL 35294-2180, U.S.A.
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A. Venkartraman;
A. Venkartraman
Department of Pathology, Center for Free Radical Biology, University of Alabama at Birmingham, AL 35294-2180, U.S.A.
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J. Crawford;
J. Crawford
Department of Pathology, Center for Free Radical Biology, University of Alabama at Birmingham, AL 35294-2180, U.S.A.
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R. Patel;
R. Patel
Department of Pathology, Center for Free Radical Biology, University of Alabama at Birmingham, AL 35294-2180, U.S.A.
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D.A. Dickinson;
D.A. Dickinson
Department of Pathology, Center for Free Radical Biology, University of Alabama at Birmingham, AL 35294-2180, U.S.A.
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E. Ulasova;
E. Ulasova
Department of Pathology, Center for Free Radical Biology, University of Alabama at Birmingham, AL 35294-2180, U.S.A.
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S. Ji;
S. Ji
Department of Pathology, Center for Free Radical Biology, University of Alabama at Birmingham, AL 35294-2180, U.S.A.
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V.M. Darley-Usmar
V.M. Darley-Usmar
1
Department of Pathology, Center for Free Radical Biology, University of Alabama at Birmingham, AL 35294-2180, U.S.A.
1To whom correspondence should be addressed (e-mail Darley@path.uab.edu).
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Publisher: Portland Press Ltd
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© 2004 Biochemical Society
2004
Biochem Soc Trans (2004) 32 (1): 151–155.
Citation
E.K. Ceaser, D.R. Moellering, S. Shiva, A. Ramachandran, A. Landar, A. Venkartraman, J. Crawford, R. Patel, D.A. Dickinson, E. Ulasova, S. Ji, V.M. Darley-Usmar; Mechanisms of signal transduction mediated by oxidized lipids: the role of the electrophile-responsive proteome. Biochem Soc Trans 1 February 2004; 32 (1): 151–155. doi: https://doi.org/10.1042/bst0320151
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