title: PTEN mediates the antioxidant effect of resveratrol at nutritionally relevant concentrations.
abstract: BACKGROUND
  Antioxidant properties of resveratrol have been intensively studied for the last years, both in vivo and in vitro. Its bioavailability after an oral dose is very low and therefore it is very important to make sure that plasma concentrations of free resveratrol are sufficient enough to be active as antioxidant.
  
  
  OBJECTIVE
  In the present study, using nutritionally relevant concentrations of resveratrol, we aim to confirm its antioxidant capacity on reducing peroxide levels and look for the molecular pathway involved in this antioxidant effect.
  
  
  METHODS
  We used mammary gland tumor cells (MCF-7), which were pretreated with different concentrations of resveratrol for 48 h, and/or a PTEN inhibitor (bpV: bipy). Hydrogen peroxide levels were determined by fluorimetry, PTEN levels and Akt phosphorylation by Western Blotting, and mRNA expression of antioxidant genes by real-time reverse transcriptase-polymerase chain reaction (RT-PCR).
  
  
  RESULTS
  Resveratrol treatment for 48 h lowered peroxide levels in MCF-7, even at low nutritional concentrations (1 nM). This effect was mediated by the activation of PTEN/Akt pathway, which resulted in an upregulation of catalase and MnSOD mRNA levels.
  
  
  CONCLUSIONS
  Resveratrol acts as an antioxidant at nutritionally relevant concentrations by inducing the expression of antioxidant enzymes, through a mechanism involving PTEN/Akt signaling pathway.
authors.affiliation: Department of Physiotherapy, Faculty of Physiotherapy, University of Valencia, Gascó Oliag Street 5, 46010 Valencia, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Inglés
authors.affiliation: Department of Physiology, Faculty of Medicine, University of Valencia, Blasco Ibañez Avenue 15, 46010 Valencia, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Gambini
authors.affiliation: Centro Biotecnologia Vegetal, Faculdade de Ciências e Tecnologia, Instituto de Biotecnologia e Bioengenharia, Universida de do Algarve, Campus de Gambelas, Edifício 8, 8005-139 Faro, Portugal.
authors.forename: M Graça
authors.initials: MG
authors.lastname: Miguel
authors.affiliation: Department of Physiology, Faculty of Medicine, University of Valencia, Blasco Ibañez Avenue 15, 46010 Valencia, Spain.
authors.forename: Vicent
authors.initials: V
authors.lastname: Bonet-Costa
authors.affiliation: Department of Physiology, Faculty of Medicine, University of Valencia, Blasco Ibañez Avenue 15, 46010 Valencia, Spain.
authors.forename: Kheira M
authors.initials: KM
authors.lastname: Abdelaziz
authors.affiliation: Department of Physiology, Faculty of Medicine, University of Valencia, Blasco Ibañez Avenue 15, 46010 Valencia, Spain.
authors.forename: Marya
authors.initials: M
authors.lastname: El Alami
authors.affiliation: Department of Physiology, Faculty of Medicine, University of Valencia, Blasco Ibañez Avenue 15, 46010 Valencia, Spain.
authors.forename: Jose
authors.initials: J
authors.lastname: Viña
authors.affiliation: Department of Physiology, Faculty of Medicine, University of Valencia, Blasco Ibañez Avenue 15, 46010 Valencia, Spain.
authors.forename: Consuelo
authors.initials: C
authors.lastname: Borrás
mesh_terms: D000975:Antioxidants / Q000494:pharmacology*; D002374:Catalase / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D061986:MCF-7 Cells; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D000077185:Resveratrol; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D013267:Stilbenes / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
chemical_list: D000975:Antioxidants; D013267:Stilbenes; D006861:Hydrogen Peroxide; D002374:Catalase; D013482:Superoxide Dismutase; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; D000077185:Resveratrol