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Digestion of whey peptide induces bioactivity on glial cells

ABSTRACT: Whey derived peptides have shown potential activity improving brain function in pathological condition. However, there is little information about their mechanism of action on glial cells, which have important immune functions in brain. Astrocytes and microglia are essential in inflammatory and oxidative defense that take place in neurodegenerative disease. In this work we evaluate antioxidant and anti-inflammatory bioactivity of whey peptide in glial cells. Peptides were formed during simulated gastrointestinal digestion (Infogest protocol), and low molecular weight (<5kDA) peptides (WPHf) attenuated reactive oxygen species (ROS) production induced by hydrogen peroxide stimulus in both cells in dose-dependent manner. WPHf induced an increase in the antioxidant glutathione (GSH) content and prevented GSH reduction induced by lipopolysaccharides (LPS) stimulus in astrocytes cells in a cell specific form. An increase in cytokine mRNA expression (TNFalpha and IL6) and nitric oxide secretion induced by LPS was attenuated by WPHf pre-treatment in both cells. The inflammatory pathway was dependent on NFkB activation. Bioactive peptide ranking analysis showed positive correlation with hydrophobicity and negative correlation with high molecular weights. The sequence identification revealed 19 peptides cross-referred with bioactive database for others functions in addition to anti-inflammatory and antioxidant. Bioactive peptides were reach in leucine, valine and tyrosine in the C-terminal region and lysine in the N-terminal region. These proteomics data bring important aspects regarding the mechanism of action in glial cells and the structural-activity relationship of whey peptides resistant to digestion.

INSTRUMENT(S): Q-Exactive (Thermo Fisher)

ORGANISM(S): Bos Taurus (ncbitaxon:9913)

SUBMITTER: Lilian Gabriely Almeida Eduarda Spagnol Sacilotto Fabiana Galland Joseane Morari Licio Augusto Velloso Bruno Cesar Rossini Juliana Santos de Espindola Lucilene Delazari dos Santos Maria Teresa Bertoldo Pacheco

PROVIDER: MSV000094457 | MassIVE | Tue Apr 02 19:43:00 BST 2024

REPOSITORIES: MassIVE

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Project description:Sourdough fermentation, owing to a mixture of yeast and Lactic Acid Bacteria (LAB), is an old biotechnology process that deeply influences the sensory, chemical features and shelf life properties of leavened baked goods. Besides a plethora of functional active metabolites, LABs are able to produce peptides from enzymatic digestion of cereals proteins; which are defined bioactive peptides having important roles in nutrition and healthcare perspective. Starting from the observation that production of peptides is a strain specific feature and that some LAB strains are more efficient in producing Low Molecular Weight peptides, L. farciminis H3 and A11 strains and L. sanfranciscensis I4 strain have been selected for their high ability to produce peptides equipped with biological activity. The peptides isolated from the respective sourdough show antioxidant and anti-inflammatory activity detected as the ability either to reduce intracellular ROS production and to decrease the expression of inflammatory markers like NF-kB and IL-1β in cultured murine macrophages. Herein solid proofs of keeping of the biological activity of the peptides in baked bread are provided to increase the literature data on biological activity in the finished products that is, till now, still scanty. Low Molecular Weight peptides from breads obtained with the LAB strains above mentioned, show the same antioxidant and anti-inflammatory activity as that observed in doughs. Mass spectrometry performed both on doughs and breads highlights a lot of peptides derived from native proteins: among these only three peptides are present in all the analyzed extracts, while a large number of peptides are strain-specific. Moreover, comparing doughs vs breads peptides, major differences can be noticed either in amino acidic composition and in proteins from which they derive. However, irrespective of the sequences, all the tested strains produce bioactive peptides equipped with antioxidant and anti-inflammatory activity

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Digestion of whey peptide induces bioactivity on glial cells

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