Opposing Effect of Naringenin and Quercetin on the Junctional Compartment of MDCK II Cells to Modulate the Tight Junction

• Published in: Nutrients Vol. 12; no. 11; p. 3285
• Main Authors: Nakashima, Mio, Hisada, Misaki, Goda, Natsuko, Tenno, Takeshi, Kotake, Ayaka, Inotsume, Yuko, Kameoka, Ikuo, Hiroaki, Hidekazu
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 27.10.2020; MDPI
• Subjects: 1-Phosphatidylinositol 3-kinase; 5′ adenosine monophosphate (AMP)-activated protein kinase; Aglycones; AMP-activated protein kinase; AMP-Activated Protein Kinases - metabolism; Animals; Antibodies; Cell culture; Chromatography; Claudin-2 - analysis; Claudin-2 - metabolism; Dogs; dynamic equilibrium of tight junction; E coli; Electrical resistivity; Electrophoresis; epithelial barrier enhancer; Epithelial cells; Epithelial Cells - drug effects; Epithelial Cells - ultrastructure; Epithelium; Flavanones - pharmacology; Flavonoids; Glycosides; Hesperidin; Inositol; Kidney - ultrastructure; Ligands; Localization; Madin Darby Canine Kidney Cells; Microscopy; Monolayers; Morphology; Naringenin; Nitrogen; Pathogens; Phosphatidylinositol 3-Kinases - metabolism; phosphatidylinositol-3-phosphate kinase; Polyacrylamide; Proteins; Quercetin; Quercetin - pharmacology; Rutin; Signal Transduction - drug effects; tight junction integrity; Tight Junctions - drug effects; Tight Junctions - physiology; Tight Junctions - ultrastructure; Two dimensional analysis; Zonula occludens-1 protein; Zonula Occludens-1 Protein - metabolism; United States > US; Japan; epithelial barrier enhancer; dynamic equilibrium of tight junction; phosphatidylinositol-3-phosphate kinase; tight junction integrity; flavonoids; 5′ adenosine monophosphate (AMP)-activated protein kinase
• ISSN: 2072-6643; 2072-6643
• DOI: 10.3390/nu12113285

Maintaining tight junction (TJ) integrity is important for epithelial cell barriers. Previously, the enhancement of TJ integrity, induced by citrus-derived flavonoids, naringin (NRG) and hesperidin (HSD), was demonstrated, but the effects of their aglycones naringenin (NAR) and hesperetin (HST), and the mechanisms, have not been systematically investigated. Here we compared three series of flavonoids related to NAR, HST, quercetin (QUE) and their glycosides with the Madin-Darby canine kidney (MDCK) II cell monolayers. The effect of flavonoids on the protein expression level of claudin (CLD)-2 and its subcellular localization were investigated. NAR, NRG, and HSD increased the CLD-2 localization at the TJ compartment, and its protein expression level. QUE and HST showed TJ-mitigating activity. Narirutin (NRT), neohesperidin (NHD) and rutin (RUT) did not affect the TJ. In addition, NAR and QUE induced an increase or decrease of the transepithelial electrical resistance (TEER) values of the MDCK II monolayers. Two known signaling pathways, phosphatidyl-inositol-3 kinase (PI3K) and 5'-AMP-activated protein kinase (AMPK), were further compared with NAR. Two-dimensional polyacrylamide electrophoresis (2D PAGE) analysis of whole-cell proteins treated with NAR, AICA-riboside (AMPK activator) and LY294002 (PI3K inhibitor) showed in both a distinct pattern. This suggests the target of NAR's CLD-2 or zonula occludens-1 (ZO-1) modulation was unique.