title: Cocoa polyphenols attenuate hydrogen peroxide-induced inhibition of gap-junction intercellular communication by blocking phosphorylation of connexin 43 via the MEK/ERK signaling pathway.
abstract: 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.
authors: Department of Agricultural Biotechnology, Seoul National University, Seoul, Republic of Korea.
authors: Dong Eun
authors: DE
authors: Lee
authors: Nam Joo
authors: NJ
authors: Kang
authors: Kyung Mi
authors: KM
authors: Lee
authors: Bo Kyung
authors: BK
authors: Lee
authors: Jong Hun
authors: JH
authors: Kim
authors: Ki Won
authors: KW
authors: Lee
authors: Hyong Joo
authors: HJ
authors: Lee
mesh_terms: D000818:Animals; D002099:Cacao / Q000737:chemistry*; D002450:Cell Communication / Q000187:drug effects*; D002460:Cell Line; D018031:Connexin 43 / Q000378:metabolism*; D005419:Flavonoids / Q000494:pharmacology*; D017629:Gap Junctions / Q000187:drug effects*; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D010636:Phenols / Q000494:pharmacology*; D010766:Phosphorylation; D010936:Plant Extracts / Q000494:pharmacology; D059808:Polyphenols; D051381:Rats
chemical_list: D018031:Connexin 43; D005419:Flavonoids; D010636:Phenols; D010936:Plant Extracts; D059808:Polyphenols; D006861:Hydrogen Peroxide