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Green tea polyphenol sensing.

Tachibana H - Proc. Jpn. Acad., Ser. B, Phys. Biol. Sci. (2011)

Bottom Line: Green tea polyphenols have emerged over the past two decades as an important dietary factor for health promotion.There is considerable evidence that tea polyphenols, in particular (-)-epigallocatechin-3-gallate (EGCG) inhibit carcinogenesis.However, the mechanisms for the cancer-preventive activity of EGCG are not completely characterized and many features remain to be elucidated.

View Article: PubMed Central - PubMed

Affiliation: Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, Fukuoka, Japan. tatibana@agr.kyushu-u.ac.jp

ABSTRACT
Green tea polyphenols have emerged over the past two decades as an important dietary factor for health promotion. There is considerable evidence that tea polyphenols, in particular (-)-epigallocatechin-3-gallate (EGCG) inhibit carcinogenesis. However, the mechanisms for the cancer-preventive activity of EGCG are not completely characterized and many features remain to be elucidated. Recently we have identified a cell-surface EGCG receptor and the relating molecules that confer EGCG responsiveness to many cancer cells at physiological concentrations. Here, we review some of the reported mechanisms for the cancer chemopreventive action of EGCG and provide an overview of several molecules that sense and manage the physiological functions of EGCG.

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Related in: MedlinePlus

Model of possible EGCG signaling pathway for anti-allergic actions through 67LR. The suppression of MRLC phosphorylation through the cell-surface binding to the 67LR contributes to the inhibitory effect of EGCG on the histamine release from basophils. The 67LR also mediates the EGCG-induced suppression of FcεRI expression in basophils by reducing ERK1/2 phosphorylation.
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fig03: Model of possible EGCG signaling pathway for anti-allergic actions through 67LR. The suppression of MRLC phosphorylation through the cell-surface binding to the 67LR contributes to the inhibitory effect of EGCG on the histamine release from basophils. The 67LR also mediates the EGCG-induced suppression of FcεRI expression in basophils by reducing ERK1/2 phosphorylation.

Mentions: Mast cells and basophils play a central role in immediate allergic reactions mediated by IgE. Binding of multivalent allergens to specific IgE attached to the FcεRI on the surface of mast cells or basophils leads to the release of both preformed and newly generated inflammatory mediators such as histamine. These mediators ultimately cause various symptoms including atopic dermatitis, bronchial asthma, and food allergy.63,64) The early phase of cell activation of mast cells and basophils includes the phosphorylation and activation of protein tyrosine kinases and their substrates, generation of the second messengers such as inositol trisphosphate and diacylglycerol, and elevation of intracellular Ca2+ levels.65,66) The late phase of the activation, which occurs after the influx of Ca2+, includes the fusion of secretory granules with the membrane and dramatic morphological changes due to remodeling of actin cytoskeleton, which undergo extensive membrane ruffling.67–69) We found that EGCG inhibited the calcium ionophore A23187-induced histamine release from the human basophilic KU812 cells and could not inhibit the increase of the intracellular Ca2+ level after stimulation with A23187.70) This result suggested that the effect of EGCG on histamine release occurs after the elevation of the intracellular Ca2+ concentration. Thr18/Ser19 phosphorylation of MRLC has been reported to be temporally correlated with degranulation in the rat basophilic RBL-2H3 cells, and the inhibition of MRLC phosphorylation has been shown to impair the degranulation.71) Although EGC, having no ability to inhibit histamine release, showed no inhibitory effect on MRLC phosphorylation, EGCG clearly reduced the level of phosphorylated MRLC.70) After treatment of KU812 cells with the anti-67LR antibody, cells were incubated with EGCG, and further challenged with A23187. The reductive effect of EGCG on the histamine release was almost completely inhibited in cells treated with the anti-67LR antibody. Experiment using such 67LR-downregulated cells revealed a significant abrogation of the inhibitory effect of EGCG on degranulation. Furthermore, the lowering effect of EGCG on the phosphorylation of MRLC was also inhibited by either treatment with the anti-67LR antibody or 67LR-knockdown. These findings indicate that the inhibitory effect of EGCG on degranulation was caused by a modification of myosin cytoskeleton through the binding of EGCG to 67LR on the cell surface (Fig. 3). When the basophilic cells were stimulated with A23187 in the presence of EGCG (25 µmol/L), membrane ruffling was inhibited and a biased F-actin accumulation was observed. Furthermore, this EGCG-induced actin remodeling was abolished in both anti-67LR antibody-treated cells and 67LR-knockdowned cells.70) Our findings indicated that EGCG-induced actin remodeling is caused by lowering MRLC phosphorylation mediated through the binding of EGCG to the 67LR. Thus, these cytoskeletal modifications may have an important role in the inhibition of histamine release by EGCG.


Green tea polyphenol sensing.

Tachibana H - Proc. Jpn. Acad., Ser. B, Phys. Biol. Sci. (2011)

Model of possible EGCG signaling pathway for anti-allergic actions through 67LR. The suppression of MRLC phosphorylation through the cell-surface binding to the 67LR contributes to the inhibitory effect of EGCG on the histamine release from basophils. The 67LR also mediates the EGCG-induced suppression of FcεRI expression in basophils by reducing ERK1/2 phosphorylation.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3066547&req=5

fig03: Model of possible EGCG signaling pathway for anti-allergic actions through 67LR. The suppression of MRLC phosphorylation through the cell-surface binding to the 67LR contributes to the inhibitory effect of EGCG on the histamine release from basophils. The 67LR also mediates the EGCG-induced suppression of FcεRI expression in basophils by reducing ERK1/2 phosphorylation.
Mentions: Mast cells and basophils play a central role in immediate allergic reactions mediated by IgE. Binding of multivalent allergens to specific IgE attached to the FcεRI on the surface of mast cells or basophils leads to the release of both preformed and newly generated inflammatory mediators such as histamine. These mediators ultimately cause various symptoms including atopic dermatitis, bronchial asthma, and food allergy.63,64) The early phase of cell activation of mast cells and basophils includes the phosphorylation and activation of protein tyrosine kinases and their substrates, generation of the second messengers such as inositol trisphosphate and diacylglycerol, and elevation of intracellular Ca2+ levels.65,66) The late phase of the activation, which occurs after the influx of Ca2+, includes the fusion of secretory granules with the membrane and dramatic morphological changes due to remodeling of actin cytoskeleton, which undergo extensive membrane ruffling.67–69) We found that EGCG inhibited the calcium ionophore A23187-induced histamine release from the human basophilic KU812 cells and could not inhibit the increase of the intracellular Ca2+ level after stimulation with A23187.70) This result suggested that the effect of EGCG on histamine release occurs after the elevation of the intracellular Ca2+ concentration. Thr18/Ser19 phosphorylation of MRLC has been reported to be temporally correlated with degranulation in the rat basophilic RBL-2H3 cells, and the inhibition of MRLC phosphorylation has been shown to impair the degranulation.71) Although EGC, having no ability to inhibit histamine release, showed no inhibitory effect on MRLC phosphorylation, EGCG clearly reduced the level of phosphorylated MRLC.70) After treatment of KU812 cells with the anti-67LR antibody, cells were incubated with EGCG, and further challenged with A23187. The reductive effect of EGCG on the histamine release was almost completely inhibited in cells treated with the anti-67LR antibody. Experiment using such 67LR-downregulated cells revealed a significant abrogation of the inhibitory effect of EGCG on degranulation. Furthermore, the lowering effect of EGCG on the phosphorylation of MRLC was also inhibited by either treatment with the anti-67LR antibody or 67LR-knockdown. These findings indicate that the inhibitory effect of EGCG on degranulation was caused by a modification of myosin cytoskeleton through the binding of EGCG to 67LR on the cell surface (Fig. 3). When the basophilic cells were stimulated with A23187 in the presence of EGCG (25 µmol/L), membrane ruffling was inhibited and a biased F-actin accumulation was observed. Furthermore, this EGCG-induced actin remodeling was abolished in both anti-67LR antibody-treated cells and 67LR-knockdowned cells.70) Our findings indicated that EGCG-induced actin remodeling is caused by lowering MRLC phosphorylation mediated through the binding of EGCG to the 67LR. Thus, these cytoskeletal modifications may have an important role in the inhibition of histamine release by EGCG.

Bottom Line: Green tea polyphenols have emerged over the past two decades as an important dietary factor for health promotion.There is considerable evidence that tea polyphenols, in particular (-)-epigallocatechin-3-gallate (EGCG) inhibit carcinogenesis.However, the mechanisms for the cancer-preventive activity of EGCG are not completely characterized and many features remain to be elucidated.

View Article: PubMed Central - PubMed

Affiliation: Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, Fukuoka, Japan. tatibana@agr.kyushu-u.ac.jp

ABSTRACT
Green tea polyphenols have emerged over the past two decades as an important dietary factor for health promotion. There is considerable evidence that tea polyphenols, in particular (-)-epigallocatechin-3-gallate (EGCG) inhibit carcinogenesis. However, the mechanisms for the cancer-preventive activity of EGCG are not completely characterized and many features remain to be elucidated. Recently we have identified a cell-surface EGCG receptor and the relating molecules that confer EGCG responsiveness to many cancer cells at physiological concentrations. Here, we review some of the reported mechanisms for the cancer chemopreventive action of EGCG and provide an overview of several molecules that sense and manage the physiological functions of EGCG.

Show MeSH
Related in: MedlinePlus