Theaflavins enhance intestinal barrier of Caco-2 Cell monolayers through the expression of AMP-activated protein kinase-mediated Occludin, Claudin-1, and ZO-1

We investigated the effect of theaflavins (TFs) on membrane barrier of Caco-2 cells. For fluorescein-transport experiments, the apparent permeability (P app ) of fluorescein in Caco-2 cells pretreated with 20 μM TFs were significantly decreased compared with that in untreated cells. Although the res...

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Published in:Bioscience, biotechnology, and biochemistry biotechnology, and biochemistry, 2015-01, Vol.79 (1), p.130-137
Main Authors: Park, Ha-Young, Kunitake, Yuri, Hirasaki, Naoto, Tanaka, Mitsuru, Matsui, Toshiro
Format: Article
Language:English
Subjects:
AMP-Activated Protein Kinases - antagonists & inhibitors
AMP-Activated Protein Kinases - genetics
AMP-Activated Protein Kinases - metabolism
AMPK
Antioxidants - pharmacology
Benzocycloheptenes - pharmacology
Biflavonoids - pharmacology
Caco-2 cell
Caco-2 Cells
Catechin - pharmacology
Cell Membrane Permeability - drug effects
Claudin-1 - agonists
Claudin-1 - genetics
Claudin-1 - metabolism
Dose-Response Relationship, Drug
Fluorescein - metabolism
Gallic Acid - analogs & derivatives
Gallic Acid - pharmacology
Gene Expression Regulation
Humans
Occludin - agonists
Occludin - genetics
Occludin - metabolism
paracellular transport
Protein Kinase Inhibitors - pharmacology
RNA, Messenger - antagonists & inhibitors
RNA, Messenger - genetics
RNA, Messenger - metabolism
Signal Transduction
Structure-Activity Relationship
theaflavins
tight junction
Tight Junctions - drug effects
Tight Junctions - metabolism
Zonula Occludens-1 Protein - agonists
Zonula Occludens-1 Protein - genetics
Zonula Occludens-1 Protein - metabolism
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Summary:We investigated the effect of theaflavins (TFs) on membrane barrier of Caco-2 cells. For fluorescein-transport experiments, the apparent permeability (P app ) of fluorescein in Caco-2 cells pretreated with 20 μM TFs were significantly decreased compared with that in untreated cells. Although the respective monomeric catechins did not show any P app reduction, purpurogallin pretreatment resulted in a significant P app reduction similar to that of TF-3′-O-gallate (TF3′G) pretreatment. This indicates that the benzotropolone moiety may play a crucial role in the P app reduction or tight junction (TJ)-closing effect induced by TFs. In TF-3′-O-gallate-pretreated Caco-2 cells, fluorescein transport was completely restored by compound C (AMPK inhibitor). In addition, TF3′G significantly increased both the mRNA and protein expression of TJ-related proteins (occludin, claudin-1, and ZO-1) as well as the phosphorylation of AMPK. It was, thus, concluded that TFs could enhance intestinal barrier function by increasing the expression of TJ-related proteins through the activation of AMPK in Caco-2 cells. Theaflavins can close the tight junction or improve the intestinal membrane barrier via AMPK activation in Caco-2 cells.
ISSN:0916-8451
1347-6947
DOI:10.1080/09168451.2014.951027