title: β-Casein(94-123)-derived peptides differently modulate production of mucins in intestinal goblet cells.
abstract: We recently reported the identification of a peptide from yoghurts with promising potential for intestinal health: the sequence (94-123) of bovine β-casein. This peptide, composed of 30 amino acid residues, maintains intestinal homoeostasis through production of the secreted mucin MUC2 and of the transmembrane-associated mucin MUC4. Our study aimed to search for the minimal sequence responsible for the biological activity of β-CN(94-123) by using several strategies based on (i) known bioactive peptides encrypted in β-CN(94-123), (ii) in silico prediction of peptides reactivity and (iii) digestion of β-CN(94-123) by enzymes of intestinal brush border membranes. The revealed sequences were tested in vitro on human intestinal mucus-producing HT29-MTX cells. We demonstrated that β-CN(108-113) (an ACE-inhibitory peptide) and β-CN(114-119) (an opioid peptide named neocasomorphin-6) up-regulated MUC4 expression whereas levels of the secreted mucins MUC2 and MUC5AC remained unchanged. The digestion of β-CN(94-123) by intestinal enzymes showed that the peptides β-CN(94-108) and β-CN(117-123) were present throughout 1·5 to 3 h of digestion, respectively. These two peptides raised MUC5AC expression while β-CN(117-123) also induced a decrease in the level of MUC2 mRNA and protein. In addition, this inhibitory effect was reproduced in airway epithelial cells. In conclusion, β-CN(94-123) is a multifunctional molecule but only the sequence of 30 amino acids has a stimulating effect on the production of MUC2, a crucial factor of intestinal protection.
authors.affiliation: INRA USC1235, INSERM U1060, CarMeN Laboratory,University Lyon-1,INSA-Lyon, IMBL, Bât. Louis Pasteur,20 av. Albert Einstein, 69621,F-69100 Villeurbanne,France.
authors.forename: Pascale
authors.initials: P
authors.lastname: Plaisancié
authors.affiliation: INRA,UMR1253 Science et Technologie du Lait et de l'Œuf,F-35000 Rennes,France.
authors.forename: Rachel
authors.initials: R
authors.lastname: Boutrou
authors.affiliation: INRA USC1235, INSERM U1060, CarMeN Laboratory,University Lyon-1,INSA-Lyon, IMBL, Bât. Louis Pasteur,20 av. Albert Einstein, 69621,F-69100 Villeurbanne,France.
authors.forename: Monique
authors.initials: M
authors.lastname: Estienne
authors.affiliation: INRA,UMR1253 Science et Technologie du Lait et de l'Œuf,F-35000 Rennes,France.
authors.forename: Gwénaële
authors.initials: G
authors.lastname: Henry
authors.affiliation: INRA,UMR1253 Science et Technologie du Lait et de l'Œuf,F-35000 Rennes,France.
authors.forename: Julien
authors.initials: J
authors.lastname: Jardin
authors.affiliation: INRA USC1235, INSERM U1060, CarMeN Laboratory,University Lyon-1,INSA-Lyon, IMBL, Bât. Louis Pasteur,20 av. Albert Einstein, 69621,F-69100 Villeurbanne,France.
authors.forename: Armelle
authors.initials: A
authors.lastname: Paquet
authors.affiliation: INRA,UMR1253 Science et Technologie du Lait et de l'Œuf,F-35000 Rennes,France.
authors.forename: Joëlle
authors.initials: J
authors.lastname: Léonil
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002364:Caseins / Q000737:chemistry / Q000494:pharmacology*; D002417:Cattle; D015870:Gene Expression / Q000187:drug effects; D020397:Goblet Cells / Q000187:drug effects / Q000378:metabolism*; D019073:HT29 Cells; D006801:Humans; D007422:Intestines / Q000166:cytology*; D008871:Microvilli / Q000201:enzymology; D008969:Molecular Sequence Data; D055271:Mucin 5AC / Q000235:genetics; D055262:Mucin-2 / Q000096:biosynthesis / Q000235:genetics; D055264:Mucin-4 / Q000096:biosynthesis; D009077:Mucins / Q000096:biosynthesis* / Q000187:drug effects*; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology*; D010447:Peptide Hydrolases / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D013552:Swine; D015014:Yogurt / Q000032:analysis
chemical_list: D002364:Caseins; C524625:MUC2 protein, human; C524658:MUC4 protein, human; C524678:MUC5AC protein, human; D055271:Mucin 5AC; D055262:Mucin-2; D055264:Mucin-4; D009077:Mucins; D010446:Peptide Fragments; D012333:RNA, Messenger; D010447:Peptide Hydrolases
keywords: ACE Angiotensin-converting enzyme; BBMV brush border membrane vesicles; BSA bovine serum albumin; CT controls; DPP IV dipeptidyl peptidase IV; ELLA Enzyme-linked lectin assay; FBS foetal bovine serum; Milk bioactive peptides; TFA trifluoroacetic acid; intestinal barrier; intestinal protection; mucus; β-CN β-casein; β-casein