Punicalagin increases glutamate absorption in differentiated Caco-2 cells by a mechanism involving gene expression regulation of an EAAT3 transporter

Biolley, C.; Tretola, M.; Bee, Giuseppe; Jud, Corinne; Silacci, Paolo

doi:10.1039/c9fo00191c

Cited by 7 publications

(4 citation statements)

References 28 publications

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“…Nevertheless, in rats receiving punicalagin as dietary supplement, punicalagin was detected in plasma and feces, suggesting that residual punicalagin may be present in feces and be absorbed by enterocytes or exert its action on enterocytes [26]. The observation that direct ellagitannins treatment can induce apoptosis, a reduction of oxidative stress and an increase in glutamate uptake following upregulation of EAAT3 glutamate-transporter gene expression [27][28][29][30], support this hypothesis. Interestingly, cell cycle arrest has also been described for proliferating Caco-2 exposed to EA, Uro-A or Uro-B [24], suggesting that ellagitannins and their metabolites may stimulate similar signaling pathways in enterocytes.…”

Section: Given the Rapid Transformation Of Ellagitannins Into Ea Inmentioning

confidence: 85%

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2019

NFSIJ

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The health benefits of pomegranate consumption have been known since the antiquity. More recently, the biological activities of pomegranate, including its anti-bacterial, antioxidant, anti-inflammatory and anticarcinogenic properties, have raised great interests in the scientific community and they have been the subject of a large number of scientific studies. Several phenolic compounds are present in various parts of the fruit, of which ellagitannins, hydrolysable tannins considered responsible for most health benefits of pomegranate. Despite all these efforts, the actual effectors remain unidentified and the mechanisms of action only partially elucidated. This is probably due to the complex catabolic pathway of these molecules that takes place in the gastrointestinal tract, involving both microbial and cellular modifications before entering the bloodstream. The diversity of the intestinal microbiota in the human population leads to the production of different metabolites in individuals, contributing to the heterogeneity of the response to dietary pomegranate assumption. This complex situation determines the need for special attention in designing studies on the action of ellagitannins on both cell cultures and animal models.

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Section: Given the Rapid Transformation Of Ellagitannins Into Ea Inmentioning

confidence: 85%

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2019

NFSIJ

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“…Cell line/Tissue References Cell lines T84 Schuier et al, 2005;Bergmann et al, 2009;Rogoll et al, 2010;Deusser et al, 2020Caco-2 Steinert et al, 2008Scherbl et al, 2014;Biolley et Abbreviation: SI, small intestine (both jejunum and ileum).…”

Section: Speciesmentioning

confidence: 99%

Review: Harmonised in vitro digestion and the Ussing chamber for investigating the effects of polyphenols on intestinal physiology in monogastrics and ruminants

Tretola¹,

Bee²,

Dohme‐Meier³

et al. 2023

animal

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“…It is known that the absorption of both exogenous and endogenous nutrients can be affected by the epithelial membrane integrity, as determined by the expression of tight-junction proteins, such as occludin, claudin and zonula occludens (6,7) . Moreover, intestinal AA absorption is also regulated by specific AA transporters located at the luminal or basolateral sides of intestinal epithelial cells (8) . Phenolic compounds, together with other extracellular stimuli, can modulate both tight-junction proteins and AA transporter expression (6)(7)(8) .…”

mentioning

confidence: 99%

“…Moreover, intestinal AA absorption is also regulated by specific AA transporters located at the luminal or basolateral sides of intestinal epithelial cells (8) . Phenolic compounds, together with other extracellular stimuli, can modulate both tight-junction proteins and AA transporter expression (6)(7)(8) . This latter property is of great interest for human and animal well-being, considering that AA are effectors of epithelial cell function (9) .…”

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confidence: 99%

Gallic acid affects intestinal-epithelial-cell integrity and selected amino-acid uptake in porcine in vitro and ex vivo permeability models

2020

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Gallic acid (GA) is widely used as a dietary supplement due to several health-promoting effects, although its effects on intestinal-epithelial-cell integrity and transport remain mostly unknown. This study aims to clarify the effects of GA on tight junctions and intestinal nutrient uptake through in-vitro and ex-vivo models. Both IPEC-J2 cells and porcine middle-jejunum segments were treated with 5 (T5), 25 (T25) and 50 (T50) µM GA and mounted in Ussing chambers to determine transepithelial resistance (TEER), claudin-1 (CLDN1), occludin (OCLN), zonula occludens-1 (ZO-1) protein (in tissues and cells) and mRNA (in cells) expression. In addition, uptake of L-Glutamate (L-Glut), L-Arginine (L-Arg), L-Lysine (L-Lys) and L-Methionine (L-Meth), together with cationic-amino-acid transporter-1 (CAT-1) and excitatory-amino-acid transporter-3 (EAAT3) expression was evaluated. No apoptosis was observed in GA-treated cells, but TEER and CLDN1 protein abundance was lower with T50 compared to untreated cells. L-Arg and L-Lys uptake was greater with T5 than with T25 and T50. Ex vivo, T50 decreased the TEER values and the protein levels of CLDN1, OCLN and ZO-1, whereas T5 and T25 only decreased CLDN1 protein expression compared to untreated tissues. Moreover, T25 increased L-Glut and L-Arg uptake, the latter confirmed by an increased protein expression of CAT-1. GA influences intestinal uptake of the tested cationic amino acids at low concentrations and decreases the intestinal-cell barrier function at high concentrations. Similarities were observed between in vitro and ex vivo, but different treatment times and structures must be considered.

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Punicalagin increases glutamate absorption in differentiated Caco-2 cells by a mechanism involving gene expression regulation of an EAAT3 transporter

Abstract: Punicalagin modulates EAAT3 gene expression in enterocytes, increasing intestinal glutamate uptake.

Cited by 7 publications

References 28 publications

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Untitled

Review: Harmonised in vitro digestion and the Ussing chamber for investigating the effects of polyphenols on intestinal physiology in monogastrics and ruminants

Gallic acid affects intestinal-epithelial-cell integrity and selected amino-acid uptake in porcine in vitro and ex vivo permeability models

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