title: Procyanidin B2 induces Nrf2 translocation and glutathione S-transferase P1 expression via ERKs and p38-MAPK pathways and protect human colonic cells against oxidative stress.
abstract: OBJECTIVE
  Procyanidin B2 (PB2) is a naturally occurring flavonoid widely found in cocoa, red wine and grape juice. Recent studies have suggested that PB2 could protect against oxidative stress- and chemical-induced injury in colonic cells by modulating the endogenous cellular defence. However, the precise mechanism for this protection is not fully understood. Herein, we examined the effect of PB2 on the expression of one of the major antioxidant/detoxificant enzymes related to intestinal protection, the glutathione S-transferase P1 (GSTP1), and the molecular mechanisms involved.
  
  
  METHODS
  Human colonic Caco-2 cells were treated with PB2 at different times and enzymatic activity, and mRNA and protein levels of GSTP1 were evaluated. The nuclear translocation of the transcription factor NF-erythroid 2-related factor (Nrf2) and the phosphorylation states of specific proteins central to intracellular signalling cascades were also investigated.
  
  
  RESULTS
  PB2 induced the expression and activity of GSTP1 and the nuclear translocation of Nrf2. Interestingly, two important signalling proteins involved in Nrf2 translocation, the extracellular signal-regulated protein kinases (ERKs) and the p38 mitogen-activated protein kinase (MAPK) were also activated. Further experiments with specific inhibitors of both pathways confirmed their critical role in the beneficial effects induced by PB2.
  
  
  CONCLUSIONS
  The present results show that PB2 protects against oxidative injury in colonic cells and up-regulate the expression of GSTP1 via a mechanism that involves ERK and p38 MAPK activation and Nrf2 translocation. These results provide a molecular basis for the potential contribution of PB2 in the prevention of oxidative stress-related intestinal injury and gut pathologies.
authors: Department of Metabolism and Nutrition, Instituto de Ciencia y Tecnologia de Alimentos y Nutricion (ICTAN-CSIC), José Antonio Novais 10, Ciudad Universitaria, 28040, Madrid, Spain.
authors: Ildefonso
authors: I
authors: Rodríguez-Ramiro
authors: Sonia
authors: S
authors: Ramos
authors: Laura
authors: L
authors: Bravo
authors: Luis
authors: L
authors: Goya
authors: Maria Ángeles
authors: MÁ
authors: Martín
mesh_terms: D000975:Antioxidants / Q000494:pharmacology; D044946:Biflavonoids / Q000494:pharmacology*; D018938:Caco-2 Cells; D002392:Catechin / Q000494:pharmacology*; D002470:Cell Survival; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism; D051549:Glutathione S-Transferase pi / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D020935:MAP Kinase Signaling System; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects*; D010766:Phosphorylation / Q000187:drug effects; D044945:Proanthocyanidins / Q000494:pharmacology*; D021381:Protein Transport; D017382:Reactive Oxygen Species; D017423:Sequence Analysis, RNA; D015854:Up-Regulation; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D000975:Antioxidants; D044946:Biflavonoids; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D044945:Proanthocyanidins; D017382:Reactive Oxygen Species; C479580:procyanidin B2; D002392:Catechin; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases