Hydrogen peroxide negatively modulates Wnt signaling through downregulation of beta-catenin.
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.
Department of Biochemistry and Molecular Biology, College of Medicine, Yeungnam University, Daegu, South Korea.
Soon Young
SY
Shin
Chang Gun
CG
Kim
Eek-Hoon
EH
Jho
Myung-Sun
MS
Rho
Yong Sik
YS
Kim
Young-Ho
YH
Kim
Young Han
YH
Lee
D048868:Adaptor Proteins, Signal Transducing; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D017077:Culture Media, Conditioned / Q000494:pharmacology; D045304:Cytochromes c / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000096:biosynthesis* / Q000378:metabolism; D053938:DNA Fragmentation; D004268:DNA-Binding Proteins / Q000378:metabolism; D000072261:Dishevelled Proteins; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism / Q000494:pharmacology*; D051821:Lymphoid Enhancer-Binding Factor 1; D010750:Phosphoproteins / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D015398:Signal Transduction; D013347:Subcellular Fractions; D015534:Trans-Activators / Q000096:biosynthesis* / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D051153:Wnt Proteins; D060508:Wnt3 Protein; D060509:Wnt3A Protein; D051176:beta Catenin
D048868:Adaptor Proteins, Signal Transducing; C495270:CTNNB1 protein, human; D017077:Culture Media, Conditioned; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; C000606578:DVL1 protein, human; D000072261:Dishevelled Proteins; D051821:Lymphoid Enhancer-Binding Factor 1; D010750:Phosphoproteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D014157:Transcription Factors; C555510:WNT3A protein, human; D051153:Wnt Proteins; D060508:Wnt3 Protein; D060509:Wnt3A Protein; D051176:beta Catenin; D045304:Cytochromes c; D006861:Hydrogen Peroxide