Transepithelial Transport of the Bioactive Tripeptide, Val-Pro-Pro, in Human Intestinal Caco-2 Cell Monolayers

Satake, Makoto; Enjoh, Masashi; Nakamura, Yasunori; Takano, Toshiaki; Kawamura, Yukio; Arai, Soichi; Shimizu, Makoto

doi:10.1271/bbb.66.378

Cited by 210 publications

(187 citation statements)

References 30 publications

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“…For instance, the tripeptide exerts chemotactic effects on fibroblasts, peripheral blood neutrophils and monocytes in cell culture systems [13][14][15] . Based on the size, the tripeptides are expected to be suitable for trans-epithelial transport 16 . Aito-Inoue et al 17 investigated the transport of Gly-Pro-Hyp across the intestinal brush-border membrane (BBM) in a porcine BBM model.…”

Section: Discussionmentioning

confidence: 99%

Inhibitory effect of collagen-derived tripeptides on dipeptidylpeptidase-IV activity

Hatanaka

Kawakami

Uraji

2014

Journal of Enzyme Inhibition and Medicinal Chemistry

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The collagen tripeptide fragments Gly-Ala-Hyp, Gly-Pro-Ala and Gly-Pro-Hyp were generated by hydrolyzing collagen from pig-skin, cattle-skin, fish-scales and chicken-feet, respectively, with Streptomyces collagenase. Collagenase treatment increased the concentration of tripeptides in the hydrolysates by 13-15% (w/w). Of the three peptides, Gly-Pro-Hyp was a true peptidic inhibitor of dipeptidylpeptidase-IV (DPP-IV), because DPP-IV could not hydrolyze the bond between Pro-Hyp. This tripeptide was a moderately competitive inhibitor (K i ¼ 4.5 mM) of DPP-IV, and its level in the collagen hydrolysates could be greatly increased (4-9% [w/w]) using Streptomyces collagenase.

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Section: Discussionmentioning

confidence: 99%

Inhibitory effect of collagen-derived tripeptides on dipeptidylpeptidase-IV activity

Hatanaka

Kawakami

Uraji

2014

Journal of Enzyme Inhibition and Medicinal Chemistry

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“…16,17 It has been suggested that the mechanism of the antihypertensive effect exerted by such tripeptides is ACE inhibition. 6,7 Sipola et al 7 reported that the BP at the end of a trial in rats that had consumed peptide-enriched fermented milk was 21 mmHg lower than the BP of rats that had consumed water, and 10 mmHg lower than the BP of rats that had consumed Calpis s .…”

Section: Discussionmentioning

confidence: 99%

Effect of ingesting sour milk fermented using Lactobacillus helveticus bacteria producing tripeptides on blood pressure in subjects with mild hypertension

Lindström²,

et al. 2004

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Angiotensin-converting enzyme (ACE) is important in the regulation of blood pressure (BP). Two tripeptides that inhibit ACE, isoleucyl-prolyl-proline (Ile-Pro-Pro) and valyl-prolyl-proline (Val-Pro-Pro), have been isolated from certain sour milks. The aim of the study reported was to evaluate the effect on BP in subjects with mild hypertension of a new sour milk containing tripeptides. The initial number of subjects was 60 (36 men, 24 women). Among the criteria for inclusion in the study were systolic BP (SBP) between 140 and 180 mmHg and/or diastolic BP (DPB) between 90 and 110 mmHg, without antihypertensive drug therapy. There were two study periods with a washout period between. All subjects were given 1.5 dl per day of a placebo (regular sour milk) or of the active product, a milk that had been fermented with Lactobacillus helveticus bacteria and contained 2.4-2.7 mg of Ile-Pro-Pro and 2.4-2.7 mg of Val-Pro-Pro per 1.5 dl. In the first phase, SBP fell 16 mmHg from baseline in the active group, 2 mmHg more than in the placebo group (P ¼ 0.0668) and no difference in DBP (P ¼ 0.92). There was a statistically significant downward trend both in SBP and DBP (P ¼ 0.0001). During the second phase, SBP fell 11 mmHg in the active group (P ¼ 0.008). The reduction in SBP was significantly larger in active than placebo group (P ¼ 0.012). In the crossover analysis combining both phases, SBP fell on average 2.6715.9 mmHg more on the active product compared with the placebo product, but this difference was not statistically significant (P ¼ 0.3111). The difference in DBP, 1.078.3 mmHg between the two test products was not significant either (P ¼ 0.4431). In conclusion, the ingestion of sour milk fermented by L. helveticus bacteria and that containing ACE inhibitory tripeptides seems to lower BP modestly.

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“…27) We examined IEC permeability to the antihypertensive tripeptide VPP, derived from bovine -casein, using Caco-2 monolayers cultured on semipermeable membranes. 28) The results suggested that VPP is transported across human IEC monolayers via the paracellular route rather than by the PepT1-mediated transport pathway (Fig. 3).…”

Section: Transport Pathways For Oligopeptidesmentioning

confidence: 93%

Interaction between Food Substances and the Intestinal Epithelium

Shimizu

2010

Bioscience, Biotechnology, and Biochemistry

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130

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The small intestine is an organ responsible for nutrient absorption, barrier functions, signal recognition/transduction, and the production of bioactive compounds. These functions are known to be regulated by such factors as hormones and cytokines, but substances contained in the daily diet are also thought to play roles as major modulators of intestinal functions. Intestinal epithelial cells (IECs), which form a monolayer covering the inside surface of the intestinal tract, are particularly important in this modulation, because they directly interact with intestinal contents, including food substances, their digests, and gut microbial components. Using cell-based in vitro assays, we investigated the food-IEC interactions at the cellular and molecular levels, and found that a variety of food substances affected the transporter activity, tight junction permeability, metabolic enzyme expression, immune functions, and so on. Modulation of the intestinal functions by dietary substances is therefore essential to promote health.

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Transepithelial Transport of the Bioactive Tripeptide, Val-Pro-Pro, in Human Intestinal Caco-2 Cell Monolayers

Cited by 210 publications

References 30 publications

Inhibitory effect of collagen-derived tripeptides on dipeptidylpeptidase-IV activity

Inhibitory effect of collagen-derived tripeptides on dipeptidylpeptidase-IV activity

Effect of ingesting sour milk fermented using Lactobacillus helveticus bacteria producing tripeptides on blood pressure in subjects with mild hypertension

Interaction between Food Substances and the Intestinal Epithelium

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