Abstract
The Wnt signal transduction pathway plays an important role in organogenesis and carcinogenesis. In an effort to better understand the action of oxidative stress-induced cellular signaling, we investigate the effect of exogenous H2O2 on the Wnt signal pathway. H2O2 decreases the amount of nuclear beta-catenin and Tcf/Lef-dependent transcription. Overexpression of Dvl-1 abrogated H2O2-induced downregulation of beta-catenin. Pretreatment with LiCl or Wnt-3a conditioned medium completely inhibited H2O2-induced release of mitochondrial cytochrome c and DNA fragmentation. These results suggest that H2O2 negatively modulates the Wnt signal pathway through downregulation of beta-catenin.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing
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Cell Line
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Cell Nucleus / metabolism
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Culture Media, Conditioned / pharmacology
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Cytochromes c / metabolism
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Cytoskeletal Proteins / biosynthesis*
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Cytoskeletal Proteins / metabolism
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DNA Fragmentation
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DNA-Binding Proteins / metabolism
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Dishevelled Proteins
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Dose-Response Relationship, Drug
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Down-Regulation*
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Humans
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Hydrogen Peroxide / metabolism
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Hydrogen Peroxide / pharmacology*
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Lymphoid Enhancer-Binding Factor 1
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Phosphoproteins / metabolism
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Proteins / metabolism
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Proto-Oncogene Proteins / metabolism*
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Signal Transduction*
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Subcellular Fractions
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Trans-Activators / biosynthesis*
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Trans-Activators / metabolism
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Transcription Factors / metabolism
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Transcription, Genetic
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Wnt Proteins
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Wnt3 Protein
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Wnt3A Protein
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beta Catenin
Substances
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Adaptor Proteins, Signal Transducing
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CTNNB1 protein, human
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Culture Media, Conditioned
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Cytoskeletal Proteins
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DNA-Binding Proteins
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DVL1 protein, human
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Dishevelled Proteins
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Lymphoid Enhancer-Binding Factor 1
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Phosphoproteins
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Proteins
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Proto-Oncogene Proteins
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Trans-Activators
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Transcription Factors
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WNT3A protein, human
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Wnt Proteins
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Wnt3 Protein
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Wnt3A Protein
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beta Catenin
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Cytochromes c
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Hydrogen Peroxide