Dataset Information

Transport of a Peptide from Bovine ?s1-Casein across Models of the Intestinal and Blood-Brain Barriers.

ABSTRACT: The effect of food components on brain growth and development has attracted increasing attention. Milk has been shown to contain peptides that deliver important signals to the brains of neonates and infants. In order to reach the brain, milk peptides have to resist proteolytic degradation in the gastrointestinal tract, cross the gastrointestinal barrier and later cross the highly selective blood-brain barrier (BBB). To investigate this, we purified and characterized endogenous peptides from bovine milk and investigated their apical to basal transport by using human intestinal Caco-2 cells and primary porcine brain endothelial cell monolayer models. Among 192 characterized milk peptides, only the ?S1-casein peptide 185PIGSENSEKTTMPLW199, and especially fragments of this peptide processed during the transport, could cross both the intestinal barrier and the BBB cell monolayer models. This peptide was also shown to resist simulated gastrointestinal digestion. This study demonstrates that a milk derived peptide can cross the major biological barriers in vitro and potentially reach the brain, where it may deliver physiological signals.

SUBMITTER: Christensen B

PROVIDER: S-EPMC7602804 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Transport of a Peptide from Bovine α<sub>s1</sub>-Casein across Models of the Intestinal and Blood-Brain Barriers.

Christensen Brian B Toth Andrea E AE Nielsen Simone S E SSE Scavenius Carsten C Petersen Steen V SV Enghild Jan J JJ Rasmussen Jan T JT Nielsen Morten S MS Sørensen Esben S ES

Nutrients 20201016 10

The effect of food components on brain growth and development has attracted increasing attention. Milk has been shown to contain peptides that deliver important signals to the brains of neonates and infants. In order to reach the brain, milk peptides have to resist proteolytic degradation in the gastrointestinal tract, cross the gastrointestinal barrier and later cross the highly selective blood-brain barrier (BBB). To investigate this, we purified and characterized endogenous peptides from bovi ...[more]

PMID: 33081105

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Project description:There is a growing interest in identifying natural food ingredients that may serve to prevent dementia such as that due to Alzheimer disease (AD). Peptides derived from food proteins have been demonstrated to have various physiological activities such as a hypotensive action. Recent findings have indicated possible associations of hypertension with AD progression, and suggest that angiotensin converting enzyme (ACE) inhibitors with potential to pass through the blood brain barrier (BBB) may reduce the risk of AD. In this study, we investigated the effect of milk peptide (CH-3) on cognitive function in AD model mice. CH-3 contains a tripeptide (methionine-lysine-proline, MKP) that has been found to have a strong ACE inhibitory effect and the potential to pass through the BBB. Adult male ddY mice were used in this study, and an animal model of AD was induced by intracerebroventricular (ICV) injection of A?1-42. CH-3 (250 mg/kg/day) or MKP (0.5 mg/kg/day) was orally administered every day starting 2 days before ICV injection. At 3 weeks after ICV injection, cognitive function was evaluated by the Morris water maze test. Brain samples were obtained after behavioral testing, and expression of inflammatory cytokines and NADPH oxidase subunits was measured by real-time quantitative RT-PCR. ICV injection of A?1-42 significantly impaired cognitive function compared with that in PBS-injected mice. Daily administration of CH-3 markedly attenuated this A?1-42-induced cognitive decline. A?1-42 injection significantly enhanced the expression of tumor necrosis factor-? (TNF-?), inducible nitric oxide synthase (iNOS) and p22phox in the mouse hippocampus compared with PBS injection, and showed a tendency to increase the expression of monocyte chemoattractant protein-1 (MCP-1), p47phox and gp91phox, whereas CH-3 treatment markedly reduced A?1-42-induced TNF-?, MCP-1, iNOS, p47phox and gp91phox expression. Finally, administration of MKP also attenuated A?1-42-induced cognitive impairment with an increase in cerebral blood flow. The present study demonstrated that repeated oral administration of CH-3 to AD model mice not only improved cognitive function but also suppressed the expression of inflammatory cytokines and production of oxidative stress, and suggests its therapeutic potential for preventing cognitive impairment in AD.

Dataset Information

Transport of a Peptide from Bovine ?s1-Casein across Models of the Intestinal and Blood-Brain Barriers.

Publications

Transport of a Peptide from Bovine α<sub>s1</sub>-Casein across Models of the Intestinal and Blood-Brain Barriers.

Similar Datasets

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