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Milk-derived bioactive peptides exhibit antioxidant activity through the Keap1-Nrf2 signaling pathway
Journal of Functional Foods ( IF 5.6 ) Pub Date : 2019-12-06 , DOI: 10.1016/j.jff.2019.103696
Federica Tonolo , Alessandra Folda , Luca Cesaro , Valeria Scalcon , Oriano Marin , Stefania Ferro , Alberto Bindoli , Maria Pia Rigobello

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.



中文翻译:

牛奶来源的生物活性肽通过Keap1-Nrf2信号通路表现出抗氧化活性

生物活性肽是相关的营养因子,具有许多功能,包括抗氧化剂,抗高血压,抗癌和抗微生物特性。本文对牛奶蛋白中存在的四种合成肽ARHPHPHLSFM(A-11-M),AV​​PYPQR(A-7-R),NPYVPR(N-6-R)和KVLPVPEK(K-8-K)进行了检测具有抗氧化性能。该化合物在ABTS和crocro分析(A-7-R和N-6-R)中显示出中等的自由基清除活性,在Caco-2细胞中(N-6-R和K-8-K)显示出对脂质过氧化的抑制作用。所有的肽,特别是K-8-K,都通过允许转录因子Nrf2从胞质溶胶到核的转运而激活Keap1-Nrf2系统。这种激活触发了抗氧化酶Trx1,TrxR1,GR,NQO1和SOD1的过表达。此外,分子建模表明,K-8-K能够阻碍Nrf2与Keap1的相互作用。报道的结果表明,这些生物活性肽在细胞中的抗氧化作用主要归因于Keap1-Nrf2信号通路的激活。

更新日期:2019-12-06
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