PMID- 19576746
OWN - NLM
STAT- MEDLINE
DCOM- 20101202
LR  - 20131121
IS  - 1873-4847 (Electronic)
IS  - 0955-2863 (Linking)
VI  - 21
IP  - 8
DP  - 2010 Aug
TI  - Cocoa polyphenols attenuate hydrogen peroxide-induced inhibition of gap-junction 
      intercellular communication by blocking phosphorylation of connexin 43 via the 
      MEK/ERK signaling pathway.
PG  - 680-6
LID - 10.1016/j.jnutbio.2009.03.014 [doi]
AB  - Cocoa, a good source of dietary antioxidative polyphenols, exhibited 
      anticarcinogenic activity in animal models, but the molecular mechanisms of the 
      chemopreventive potential of cocoa remain unclear. Inhibition of gap-junction 
      intercellular communication (GJIC) is strongly related to tumorigenesis. Cocoa 
      polyphenol extracts (CPE) dose dependently attenuated hydrogen peroxide 
      (H(2)O(2))-induced inhibition of GJIC in rat liver epithelial (RLE) cells. CPE 
      inhibited the H(2)O(2)-induced phosphorylation and internalization of connexin 
      43, which is a regulating protein of GJIC in RLE cells. The H(2)O(2)-induced 
      accumulation of reactive oxygen species and activation of extracellular 
      signal-regulated kinase were inhibited by CPE treatment. However, CPE did not 
      block H(2)O(2)-induced phosphorylation of p38 mitogen-activated protein kinase. 
      An ex vivo kinase assay demonstrated that CPE inhibited the H(2)O(2)-induced 
      mitogen-activated protein kinase/extracellular signal-regulated kinase kinase 
      (MEK) 1 activity in RLE cell lysates. Ex vivo pull-down assay data revealed that 
      CPE directly bound with MEK1 to inhibit MEK1 activity. These results indicate 
      that CPE protects against the H(2)O(2)-induced inhibition of GJIC through 
      antioxidant activity and direct inhibition of MEK activity, which may contribute 
      to its chemopreventive potential.
CI  - Copyright 2010 Elsevier Inc. All rights reserved.
FAU - Lee, Dong Eun
AU  - Lee DE
AD  - Department of Agricultural Biotechnology, Seoul National University, Seoul, 
      Republic of Korea.
FAU - Kang, Nam Joo
AU  - Kang NJ
FAU - Lee, Kyung Mi
AU  - Lee KM
FAU - Lee, Bo Kyung
AU  - Lee BK
FAU - Kim, Jong Hun
AU  - Kim JH
FAU - Lee, Ki Won
AU  - Lee KW
FAU - Lee, Hyong Joo
AU  - Lee HJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090702
PL  - United States
TA  - J Nutr Biochem
JT  - The Journal of nutritional biochemistry
JID - 9010081
RN  - 0 (Connexin 43)
RN  - 0 (Flavonoids)
RN  - 0 (Phenols)
RN  - 0 (Plant Extracts)
RN  - 0 (Polyphenols)
RN  - BBX060AN9V (Hydrogen Peroxide)
SB  - IM
MH  - Animals
MH  - Cacao/*chemistry
MH  - Cell Communication/*drug effects
MH  - Cell Line
MH  - Connexin 43/*metabolism
MH  - Flavonoids/*pharmacology
MH  - Gap Junctions/*drug effects
MH  - Hydrogen Peroxide/*pharmacology
MH  - MAP Kinase Signaling System/*drug effects
MH  - Phenols/*pharmacology
MH  - Phosphorylation
MH  - Plant Extracts/pharmacology
MH  - Polyphenols
MH  - Rats
EDAT- 2009/07/07 09:00
MHDA- 2010/12/14 06:00
CRDT- 2009/07/07 09:00
PHST- 2008/06/18 00:00 [received]
PHST- 2009/03/20 00:00 [revised]
PHST- 2009/03/26 00:00 [accepted]
PHST- 2009/07/07 09:00 [entrez]
PHST- 2009/07/07 09:00 [pubmed]
PHST- 2010/12/14 06:00 [medline]
AID - S0955-2863(09)00083-7 [pii]
AID - 10.1016/j.jnutbio.2009.03.014 [doi]
PST - ppublish
SO  - J Nutr Biochem. 2010 Aug;21(8):680-6. doi: 10.1016/j.jnutbio.2009.03.014. Epub 
      2009 Jul 2.