Tryptophan from human milk induces oxidative stress and upregulates the Nrf-2-mediated stress response in human intestinal cell lines

Ingrid Elisia, Apollinaire Tsopmo, James K. Friel, William Diehl-Jones, David D. Kitts

Research output: Contribution to journalJournal Articlepeer-review

15 Citations (Scopus)

Abstract

Chemical screening of digested human milk protein using the oxygen radical absorbance capacity (ORAC FL) antioxidant assay confirmed the presence of a peptide fraction (PF23) with high antioxidant activity [5.53 mmol Trolox equivalents (TE)/g] that contained tryptophan as a main component. We evaluated the effects of both PF23 and tryptophan alone on the modulation of oxidative stress in cultured intestinal cells using a dichlorofluorescein diacetate probe. Despite the high ORAC FL value, PF23 enhanced (P< 0.05) 2, 2'-azobis (2-amidinopropane) dihydrochloride (peroxyl radical generator)-induced intracellular oxidation in the Caco-2 human adenocarcinoma cell line, suggesting prooxidant activity. Compared to selected peptide fractions with relatively lower ORAC FL values, PF23 induced oxidative stress more than all other peptide fractions tested (P< 0.05) and contained more tryptophan than the others (P< 0.05). Similar prooxidant activity was observed for tryptophan when it was added to culture medium for both the Caco-2 cells and FHs 74 Int primary fetal enterocytes, while also exhibiting a high ORAC FL value (9.69 mmol TE/g). The effect of tryptophan that involves activation of the Nrf-2 pathway and transcription of antioxidant enzymes was therefore investigated in FHs 74 Int cells. Exposure of infant intestinal cells to tryptophan resulted in Nrf-2 activation and an increase in the gene transcript level of glutathione peroxidase 2. We conclude that tryptophan-induced oxidative stress associated with tryptophan-containing milk peptides induces an adaptive response that involves the activation of the antioxidant responsive signaling pathway in intestinal cells.

Original languageEnglish
Pages (from-to)1417-1423
Number of pages7
JournalJournal of Nutrition
Volume141
Issue number8
DOIs
Publication statusPublished - 1 Aug. 2011

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