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Quercetin enhances intestinal barrier function through the assembly of zonula [corrected] occludens-2, occludin, and claudin-1 and the expression of claudin-4 in Caco-2 cells.
J Nutr. 2009 May; 139(5):965-74.JN

Abstract

Dietary flavonoids provide various beneficial effects for our health. We investigated the promotive effects of quercetin and myricetin on the intestinal barrier function in human intestinal Caco-2 cell monolayers. Transepithelial electrical resistance (TER) across the monolayers increased rapidly during incubation with quercetin, peaking at 6 h. Lucifer yellow flux, a paracellular marker, was dose-dependently lower after quercetin and myricetin treatments, although quercetin exhibited a more potent effect. Immunoblot analysis of tight junction (TJ) proteins revealed that zonula occludens (ZO)-2, occludin, and claudin-1 were distributed to the actin cytoskeleton fraction by quercetin without increasing their respective whole-cell levels and this distribution was correlated with the increases in TER. The claudin-4 level was elevated by quercetin in both the cytoskeleton fraction and whole cells after 12 h. Confocal microscopy showed the assembly of claudin-1 and -4 at the TJ by quercetin. An inhibitor of protein kinase Cdelta (PKCdelta), rottlerin, enhanced the barrier function with changes in the distribution and expression of TJ proteins in a manner very similar to that of quercetin. Phosphorylation of PKCdelta indicating the enzymatic activity in the cells was decreased by quercetin after 1 h. In the kinase assay, quercetin exhibits direct inhibition of the PKCdelta isoform. This study demonstrates that quercetin enhances the intestinal barrier function through the assembly of ZO-2, occludin, and claudin-1 by inhibiting PKCdelta and the increase in claudin-4 expression has an additional role after 12 h.

Authors+Show Affiliations

Division of Applied Bioscience, Research Faculty of Agriculture, Hokkaido University Kita-9, Nishi-9, Kita-ku, Sapporo 060-8589, Japan.No affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

19297429

Citation

Suzuki, Takuya, and Hiroshi Hara. "Quercetin Enhances Intestinal Barrier Function Through the Assembly of Zonula [corrected] Occludens-2, Occludin, and Claudin-1 and the Expression of Claudin-4 in Caco-2 Cells." The Journal of Nutrition, vol. 139, no. 5, 2009, pp. 965-74.
Suzuki T, Hara H. Quercetin enhances intestinal barrier function through the assembly of zonula [corrected] occludens-2, occludin, and claudin-1 and the expression of claudin-4 in Caco-2 cells. J Nutr. 2009;139(5):965-74.
Suzuki, T., & Hara, H. (2009). Quercetin enhances intestinal barrier function through the assembly of zonula [corrected] occludens-2, occludin, and claudin-1 and the expression of claudin-4 in Caco-2 cells. The Journal of Nutrition, 139(5), 965-74. https://doi.org/10.3945/jn.108.100867
Suzuki T, Hara H. Quercetin Enhances Intestinal Barrier Function Through the Assembly of Zonula [corrected] Occludens-2, Occludin, and Claudin-1 and the Expression of Claudin-4 in Caco-2 Cells. J Nutr. 2009;139(5):965-74. PubMed PMID: 19297429.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Quercetin enhances intestinal barrier function through the assembly of zonula [corrected] occludens-2, occludin, and claudin-1 and the expression of claudin-4 in Caco-2 cells. AU - Suzuki,Takuya, AU - Hara,Hiroshi, Y1 - 2009/03/18/ PY - 2009/3/20/entrez PY - 2009/3/20/pubmed PY - 2009/5/2/medline SP - 965 EP - 74 JF - The Journal of nutrition JO - J Nutr VL - 139 IS - 5 N2 - Dietary flavonoids provide various beneficial effects for our health. We investigated the promotive effects of quercetin and myricetin on the intestinal barrier function in human intestinal Caco-2 cell monolayers. Transepithelial electrical resistance (TER) across the monolayers increased rapidly during incubation with quercetin, peaking at 6 h. Lucifer yellow flux, a paracellular marker, was dose-dependently lower after quercetin and myricetin treatments, although quercetin exhibited a more potent effect. Immunoblot analysis of tight junction (TJ) proteins revealed that zonula occludens (ZO)-2, occludin, and claudin-1 were distributed to the actin cytoskeleton fraction by quercetin without increasing their respective whole-cell levels and this distribution was correlated with the increases in TER. The claudin-4 level was elevated by quercetin in both the cytoskeleton fraction and whole cells after 12 h. Confocal microscopy showed the assembly of claudin-1 and -4 at the TJ by quercetin. An inhibitor of protein kinase Cdelta (PKCdelta), rottlerin, enhanced the barrier function with changes in the distribution and expression of TJ proteins in a manner very similar to that of quercetin. Phosphorylation of PKCdelta indicating the enzymatic activity in the cells was decreased by quercetin after 1 h. In the kinase assay, quercetin exhibits direct inhibition of the PKCdelta isoform. This study demonstrates that quercetin enhances the intestinal barrier function through the assembly of ZO-2, occludin, and claudin-1 by inhibiting PKCdelta and the increase in claudin-4 expression has an additional role after 12 h. SN - 1541-6100 UR - https://www.unboundmedicine.com/medline/citation/19297429/Quercetin_enhances_intestinal_barrier_function_through_the_assembly_of_zonula_[corrected]_occludens_2_occludin_and_claudin_1_and_the_expression_of_claudin_4_in_Caco_2_cells_ L2 - https://academic.oup.com/jn/article-lookup/doi/10.3945/jn.108.100867 DB - PRIME DP - Unbound Medicine ER -