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The methionine precursor dl-2-hydroxy-(4-methylthio)butanoic acid protects intestinal epithelial barrier function
Authors:Raquel Martín-Venegas  MTeresa Brufau  Ana Maria Guerrero-Zamora  Yves Mercier  Pierre-André Geraert  Ruth Ferrer
Affiliation:1. Departament de Fisiologia, Facultat de Farmàcia, Universitat de Barcelona, av. Joan XXIII s/n, 08028 Barcelona, Spain;2. Adisseo France S.A.S., 10 Place du Général de Gaulle, 92160 Antony, France
Abstract:dl-2-hydroxy-(4-methylthio)butanoic acid (HMTBA) is a source of dietary methionine (Met) that is widely used in poultry nutrition. We have previously shown that HMTBA is preferentially diverted to the transsulfuration pathway, which gives antioxidant metabolites such as taurine and glutathione. Therefore, here we hypothesize that this Met source can protect epithelial barrier function in an in vitro model of intestinal inflammation of Caco-2 cells. The results show that HMTBA prevents the increase in paracellular permeability induced by H2O2 or tumour necrosis factor-α. This effect can be attributed to the increased production of taurine and reduced glutathione. Similar results were obtained for dl-Met, although the protective role of the amino acid was less pronounced than that of the hydroxy analogue. In conclusion, the diversion to the transsulfuration pathway means that this Met precursor is of greater value than previously thought, due to its capacity to improve intestinal homeostasis and the quality of poultry products destined for human consumption.
Keywords:BSA  bovine serum albumin  DHA  docosahexaenoic acid  DMEM  Dulbecco&rsquo  s Modified Eagle Medium  FBS  foetal bovine serum  GSH  glutathione  GSSG  glutathione disulfide  HMTBA  dl-2-hydroxy-(4-methylthio)butanoic acid  HEPES  4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid  Hcy  homocysteine  H2O2  hydrogen peroxide  KMB  2-keto-(4-methylthio)butanoic acid  LDH  lactate dehydrogenase  Met  methionine  MCT1  monocarboxylate transporter 1  MLCK  myosin light chain kinase  MES  2-(N-morpholino)ethanesulfonic acid  PBS  phosphate buffered saline  PAG  dl-propargyl glycine  PP  paracellular permeability  rGSH  reduced glutathione  ROS  reactive oxygen species  RNS  reactive nitrogen species  Tau  taurine  TER  transepithelial electrical resistance  TJ  tight junctions  TNF-α  tumour necrosis factor-α  ZO  zona occludens
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