Milk-derived bioactive peptides exhibit antioxidant activity through the Keap1-Nrf2 signaling pathway

Bioactive peptides are relevant nutritional factors that exhibit many functions including antioxidant, antihypertensive, anticancer and antimicrobial properties. In this paper, four synthetic peptides ARHPHPHLSFM (A-11-M), AVPYPQR (A-7-R), NPYVPR (N-6-R) and KVLPVPEK (K-8-K) with sequences present i...

Full description

Bibliographic Details
Main Authors: Federica Tonolo, Alessandra Folda, Luca Cesaro, Valeria Scalcon, Oriano Marin, Stefania Ferro, Alberto Bindoli, Maria Pia Rigobello
Format: Article
Language:English
Published: Elsevier 2020-01-01
Series:Journal of Functional Foods
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S1756464619306206
_version_ 1818728235708448768
author Federica Tonolo
Alessandra Folda
Luca Cesaro
Valeria Scalcon
Oriano Marin
Stefania Ferro
Alberto Bindoli
Maria Pia Rigobello
author_facet Federica Tonolo
Alessandra Folda
Luca Cesaro
Valeria Scalcon
Oriano Marin
Stefania Ferro
Alberto Bindoli
Maria Pia Rigobello
author_sort Federica Tonolo
collection DOAJ
description Bioactive peptides are relevant nutritional factors that exhibit many functions including antioxidant, antihypertensive, anticancer and antimicrobial properties. In this paper, four synthetic peptides ARHPHPHLSFM (A-11-M), AVPYPQR (A-7-R), NPYVPR (N-6-R) and KVLPVPEK (K-8-K) with sequences present in milk proteins were examined for their antioxidant properties. The compounds show moderate free radical scavenging activity in the ABTS and crocin assays (A-7-R and N-6-R) and lipid peroxidation inhibition in Caco-2 cells (N-6-R and K-8-K). All peptides, in particular K-8-K, activate the Keap1-Nrf2 system by allowing the translocation of the transcription factor Nrf2 from the cytosol to nucleus. This activation triggers the overexpression of the antioxidant enzymes Trx1, TrxR1, GR, NQO1 and SOD1. Furthermore, molecular modeling shows that K-8-K is able to hinder the interaction of Nrf2 with Keap1. The reported results show that the antioxidant action in cells of these bioactive peptides is mostly due to the activation of Keap1-Nrf2 signaling pathway.
first_indexed 2024-12-17T22:26:46Z
format Article
id doaj.art-e4e00acc2f0a4334833d1dd749678596
institution Directory Open Access Journal
issn 1756-4646
language English
last_indexed 2024-12-17T22:26:46Z
publishDate 2020-01-01
publisher Elsevier
record_format Article
series Journal of Functional Foods
spelling doaj.art-e4e00acc2f0a4334833d1dd7496785962022-12-21T21:30:19ZengElsevierJournal of Functional Foods1756-46462020-01-0164103696Milk-derived bioactive peptides exhibit antioxidant activity through the Keap1-Nrf2 signaling pathwayFederica Tonolo0Alessandra Folda1Luca Cesaro2Valeria Scalcon3Oriano Marin4Stefania Ferro5Alberto Bindoli6Maria Pia Rigobello7University of Padova, Department of Biomedical Sciences, via Ugo Bassi 58/b, 35131 Padova, ItalyUniversity of Padova, Department of Biomedical Sciences, via Ugo Bassi 58/b, 35131 Padova, ItalyUniversity of Padova, Department of Biomedical Sciences, via Ugo Bassi 58/b, 35131 Padova, ItalyUniversity of Padova, Department of Biomedical Sciences, via Ugo Bassi 58/b, 35131 Padova, ItalyUniversity of Padova, Department of Biomedical Sciences, via Ugo Bassi 58/b, 35131 Padova, ItalyUniversity of Padova, Department of Biomedical Sciences, via Ugo Bassi 58/b, 35131 Padova, ItalyInstitute of Neuroscience, CNR, viale G. Colombo 3, 35131 Padova, ItalyUniversity of Padova, Department of Biomedical Sciences, via Ugo Bassi 58/b, 35131 Padova, Italy; Corresponding author.Bioactive peptides are relevant nutritional factors that exhibit many functions including antioxidant, antihypertensive, anticancer and antimicrobial properties. In this paper, four synthetic peptides ARHPHPHLSFM (A-11-M), AVPYPQR (A-7-R), NPYVPR (N-6-R) and KVLPVPEK (K-8-K) with sequences present in milk proteins were examined for their antioxidant properties. The compounds show moderate free radical scavenging activity in the ABTS and crocin assays (A-7-R and N-6-R) and lipid peroxidation inhibition in Caco-2 cells (N-6-R and K-8-K). All peptides, in particular K-8-K, activate the Keap1-Nrf2 system by allowing the translocation of the transcription factor Nrf2 from the cytosol to nucleus. This activation triggers the overexpression of the antioxidant enzymes Trx1, TrxR1, GR, NQO1 and SOD1. Furthermore, molecular modeling shows that K-8-K is able to hinder the interaction of Nrf2 with Keap1. The reported results show that the antioxidant action in cells of these bioactive peptides is mostly due to the activation of Keap1-Nrf2 signaling pathway.http://www.sciencedirect.com/science/article/pii/S1756464619306206Bioactive peptidesAntioxidantsOxidative stressNrf2
spellingShingle Federica Tonolo
Alessandra Folda
Luca Cesaro
Valeria Scalcon
Oriano Marin
Stefania Ferro
Alberto Bindoli
Maria Pia Rigobello
Milk-derived bioactive peptides exhibit antioxidant activity through the Keap1-Nrf2 signaling pathway
Journal of Functional Foods
Bioactive peptides
Antioxidants
Oxidative stress
Nrf2
title Milk-derived bioactive peptides exhibit antioxidant activity through the Keap1-Nrf2 signaling pathway
title_full Milk-derived bioactive peptides exhibit antioxidant activity through the Keap1-Nrf2 signaling pathway
title_fullStr Milk-derived bioactive peptides exhibit antioxidant activity through the Keap1-Nrf2 signaling pathway
title_full_unstemmed Milk-derived bioactive peptides exhibit antioxidant activity through the Keap1-Nrf2 signaling pathway
title_short Milk-derived bioactive peptides exhibit antioxidant activity through the Keap1-Nrf2 signaling pathway
title_sort milk derived bioactive peptides exhibit antioxidant activity through the keap1 nrf2 signaling pathway
topic Bioactive peptides
Antioxidants
Oxidative stress
Nrf2
url http://www.sciencedirect.com/science/article/pii/S1756464619306206
work_keys_str_mv AT federicatonolo milkderivedbioactivepeptidesexhibitantioxidantactivitythroughthekeap1nrf2signalingpathway
AT alessandrafolda milkderivedbioactivepeptidesexhibitantioxidantactivitythroughthekeap1nrf2signalingpathway
AT lucacesaro milkderivedbioactivepeptidesexhibitantioxidantactivitythroughthekeap1nrf2signalingpathway
AT valeriascalcon milkderivedbioactivepeptidesexhibitantioxidantactivitythroughthekeap1nrf2signalingpathway
AT orianomarin milkderivedbioactivepeptidesexhibitantioxidantactivitythroughthekeap1nrf2signalingpathway
AT stefaniaferro milkderivedbioactivepeptidesexhibitantioxidantactivitythroughthekeap1nrf2signalingpathway
AT albertobindoli milkderivedbioactivepeptidesexhibitantioxidantactivitythroughthekeap1nrf2signalingpathway
AT mariapiarigobello milkderivedbioactivepeptidesexhibitantioxidantactivitythroughthekeap1nrf2signalingpathway