title: Resveratrol stimulates cyclic AMP response element mediated gene transcription.
abstract: METHODS
  Many intracellular effects have been attributed to resveratrol, a polyphenolic phytoalexin found in grapes and in other plants, including the direct regulation of transcription. Here, we have analyzed the impact of resveratrol on gene transcription regulated by the cyclic AMP response element (CRE).
  
  
  RESULTS
  Transcription of a chromatin-embedded reporter gene with CREs in its regulatory region was significantly elevated in resveratrol-treated 293 human embryonic kidney cells, hepatoma cells and neural stem cells. The CRE thus functions as resveratrol-responsive element. The polyphenols quercetin and naringenin also stimulated CRE-mediated gene transcription, but not in the range of resveratrol. The polyphenol curcumin, in contrast, had no effect upon CRE-regulated transcription. In addition, resveratrol stimulation upregulated the transcriptional activation potentials of the CRE-binding proteins (CREB) and activating transcription factor 2 (ATF2).
  
  
  CONCLUSIONS
  CREB exhibits cytoprotective activity by stimulating CRE-regulated genes, while ATF2 has been identified as a tumor suppressor. The fact that resveratrol upregulates CRE-mediated gene transcription and enhances the transcriptional activation potentials of CREB and ATF2 suggests that cytoprotective and tumor suppressive activities of resveratrol may rely-at least in part-on the stimulation of CREB- and ATF2-controlled target genes.
authors.affiliation: Department of Medical Biochemistry and Molecular Biology, Medical Faculty, Saarland University, Homburg, Germany.
authors.forename: Gerald
authors.initials: G
authors.lastname: Thiel
authors.affiliation: Department of Medical Biochemistry and Molecular Biology, Medical Faculty, Saarland University, Homburg, Germany.
authors.forename: Oliver G
authors.initials: OG
authors.lastname: Rössler
mesh_terms: D051698:Activating Transcription Factor 2 / Q000235:genetics; D016588:Anticarcinogenic Agents / Q000494:pharmacology; D002478:Cells, Cultured; D003474:Curcumin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics; D044950:Flavanones / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects*; D057809:HEK293 Cells / Q000187:drug effects; D056945:Hep G2 Cells / Q000187:drug effects; D006801:Humans; D058953:Neural Stem Cells / Q000187:drug effects; D011794:Quercetin / Q000494:pharmacology; D020218:Response Elements / Q000187:drug effects*; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D015533:Transcriptional Activation; D015854:Up-Regulation / Q000187:drug effects
chemical_list: C497105:ATF2 protein, human; D051698:Activating Transcription Factor 2; D016588:Anticarcinogenic Agents; C115163:CREB1 protein, human; D017362:Cyclic AMP Response Element-Binding Protein; D044950:Flavanones; D013267:Stilbenes; D011794:Quercetin; D000242:Cyclic AMP; C005273:naringenin; D003474:Curcumin; D000077185:Resveratrol
keywords: ATF2; CREB; Polyphenol; Resveratrol; cAMP response element