title: Degradation of coeliac disease-inducing rye secalin by germinating cereal enzymes: diminishing toxic effects in intestinal epithelial cells.
abstract: Currently the only treatment for coeliac disease is a lifelong gluten-free diet excluding food products containing wheat, rye and barley. There is, however, only scarce evidence as to harmful effects of rye in coeliac disease. To confirm the assumption that rye should be excluded from the coeliac patient's diet, we now sought to establish whether rye secalin activates toxic reactions in vitro in intestinal epithelial cell models as extensively as wheat gliadin. Further, we investigated the efficacy of germinating cereal enzymes from oat, wheat and barley to hydrolyse secalin into short fragments and whether secalin-induced harmful effects can be reduced by such pretreatment. In the current study, secalin elicited toxic reactions in intestinal Caco-2 epithelial cells similarly to gliadin: it induced epithelial cell layer permeability, tight junctional protein occludin and ZO-1 distortion and actin reorganization. In high-performance liquid chromatography and mass spectroscopy (HPLC-MS), germinating barley enzymes provided the most efficient degradation of secalin and gliadin peptides and was thus selected for further in vitro analysis. After germinating barley enzyme pretreatment, all toxic reactions induced by secalin were ameliorated. We conclude that germinating enzymes from barley are particularly efficient in the degradation of rye secalin. In future, these enzymes might be utilized as a novel medical treatment for coeliac disease or in food processing in order to develop high-quality coeliac-safe food products.
authors.affiliation: Pediatric Research Center, Medical School, University of Tampere, Tampere, Finland.
authors.forename: S M
authors.initials: SM
authors.lastname: Stenman
authors.forename: K
authors.initials: K
authors.lastname: Lindfors
authors.forename: J I
authors.initials: JI
authors.lastname: Venäläinen
authors.forename: A
authors.initials: A
authors.lastname: Hautala
authors.forename: P T
authors.initials: PT
authors.lastname: Männistö
authors.forename: J A
authors.initials: JA
authors.lastname: Garcia-Horsman
authors.forename: A
authors.initials: A
authors.lastname: Kaukovirta-Norja
authors.forename: S
authors.initials: S
authors.lastname: Auriola
authors.forename: T
authors.initials: T
authors.lastname: Mauriala
authors.forename: M
authors.initials: M
authors.lastname: Mäki
authors.forename: K
authors.initials: K
authors.lastname: Kaukinen
mesh_terms: D018554:Avena / Q000201:enzymology; D018938:Caco-2 Cells; D002446:Celiac Disease / Q000276:immunology*; D002462:Cell Membrane / Q000187:drug effects; D003599:Cytoskeleton / Q000187:drug effects; D002523:Edible Grain / Q000201:enzymology*; D017097:Electric Impedance; D018525:Germination; D005903:Gliadin / Q000276:immunology / Q000378:metabolism; D005983:Glutens / Q000276:immunology / Q000378:metabolism* / Q000633:toxicity*; D001467:Hordeum / Q000201:enzymology; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects*; D008565:Membrane Proteins / Q000378:metabolism; D062793:Occludin; D010434:Pepsin A / Q000378:metabolism; D010446:Peptide Fragments / Q000032:analysis / Q000378:metabolism / Q000494:pharmacology; D010447:Peptide Hydrolases / Q000378:metabolism; D010539:Permeability / Q000187:drug effects; D010750:Phosphoproteins / Q000378:metabolism; D012434:Secale / Q000737:chemistry*; D019108:Tight Junctions / Q000187:drug effects / Q000378:metabolism; D014908:Triticum / Q000737:chemistry / Q000201:enzymology; D014357:Trypsin / Q000378:metabolism; D062826:Zonula Occludens-1 Protein
chemical_list: D008565:Membrane Proteins; C568985:OCLN protein, human; D062793:Occludin; D010446:Peptide Fragments; D010750:Phosphoproteins; C569042:TJP1 protein, human; D062826:Zonula Occludens-1 Protein; D005983:Glutens; D005903:Gliadin; D010447:Peptide Hydrolases; D014357:Trypsin; D010434:Pepsin A