PMID- 22042007
OWN - NLM
STAT- MEDLINE
DCOM- 20130208
LR  - 20220317
IS  - 1436-6215 (Electronic)
IS  - 1436-6207 (Linking)
VI  - 51
IP  - 7
DP  - 2012 Oct
TI  - 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.
PG  - 881-92
AB  - PURPOSE: 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.
FAU - Rodriguez-Ramiro, Ildefonso
AU  - Rodriguez-Ramiro I
AD  - Department of Metabolism and Nutrition, Instituto de Ciencia y Tecnologia de 
      Alimentos y Nutricion (ICTAN-CSIC), Jose Antonio Novais 10, Ciudad Universitaria, 
      28040, Madrid, Spain.
FAU - Ramos, Sonia
AU  - Ramos S
FAU - Bravo, Laura
AU  - Bravo L
FAU - Goya, Luis
AU  - Goya L
FAU - Martin, Maria Angeles
AU  - Martin MA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20111101
PL  - Germany
TA  - Eur J Nutr
JT  - European journal of nutrition
JID - 100888704
RN  - 0 (Antioxidants)
RN  - 0 (Biflavonoids)
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (NFE2L2 protein, human)
RN  - 0 (Proanthocyanidins)
RN  - 0 (Reactive Oxygen Species)
RN  - 29106-49-8 (procyanidin B2)
RN  - 8R1V1STN48 (Catechin)
RN  - EC 2.5.1.18 (GSTP1 protein, human)
RN  - EC 2.5.1.18 (Glutathione S-Transferase pi)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Antioxidants/pharmacology
MH  - Biflavonoids/*pharmacology
MH  - Caco-2 Cells
MH  - Catechin/*pharmacology
MH  - Cell Survival
MH  - Extracellular Signal-Regulated MAP Kinases/genetics/metabolism
MH  - Glutathione S-Transferase pi/genetics/*metabolism
MH  - Humans
MH  - *MAP Kinase Signaling System
MH  - NF-E2-Related Factor 2/genetics/*metabolism
MH  - Oxidative Stress/*drug effects
MH  - Phosphorylation/drug effects
MH  - Proanthocyanidins/*pharmacology
MH  - Protein Transport
MH  - Reactive Oxygen Species
MH  - Sequence Analysis, RNA
MH  - Up-Regulation
MH  - p38 Mitogen-Activated Protein Kinases/genetics/metabolism
EDAT- 2011/11/02 06:00
MHDA- 2013/02/09 06:00
CRDT- 2011/11/02 06:00
PHST- 2011/07/26 00:00 [received]
PHST- 2011/10/19 00:00 [accepted]
PHST- 2011/11/02 06:00 [entrez]
PHST- 2011/11/02 06:00 [pubmed]
PHST- 2013/02/09 06:00 [medline]
AID - 10.1007/s00394-011-0269-1 [doi]
PST - ppublish
SO  - Eur J Nutr. 2012 Oct;51(7):881-92. doi: 10.1007/s00394-011-0269-1. Epub 2011 Nov 
      1.