301. Involvement of Nrf2 and Keap1 in the activation of antioxidant responsive element (ARE) by chemopreventive agent peptides from soft-shelled turtle.
- Author
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Wang, Nan, Wang, Wei, Sadiq, Faizan Ahmed, Wang, Shilei, Caiqin, Liu, and Jianchang, Jin
- Subjects
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SOFT-shelled turtles , *PEPTIDES , *GENE enhancers , *XENOBIOTICS , *HYDROGEN bonding , *OXIDATIVE stress - Abstract
The peptide EDYGA was docked to the active pocket of Keap1 Kelch domain, three hydrogen bonds were found, the pocket of Keap1 Kelch domain are H bond donor, and EDYGA was hydrogen bond acceptor. • Peptide EDYGA was the most potent ARE-luciferase inducer. • EDYGA enhanced Nrf2 level by stabilizing Nrf2 by down regulating Keap1. • EDYGA was docked to the active pocket with three hydrogen bonds. The antioxidant response element (ARE) is a cis-acting enhancer sequence located in the region containing genes related to antioxidant and detoxification. Under oxidative stress, the induction of nuclear factor-E2-related factor 2 (Nrf2)/ARE is considered as a fundamental process involved in defending reactive oxygen species (ROS) and providing protection against toxic xenobiotics. In this study, we obtained seven antioxidant peptides from soft-shelled turtle and concluded that Glu-Asp-Tyr-Gly-Ala (EDYGA) is the most potent ARE-luciferase inducer. To gain fundamental insights into the role of EDYGA in oxidative stress, we evaluated the effects of EDYGA on the Nrf2/Keap1 system in HepG 2 cells. The results revealed that EDYGA modulated the Nrf2/ARE pathway by enhancing Nrf2 level through the stabilization of Nrf2, which was accomplished by a decrease in the level of Keap1. These actions eventually led to an increase in nuclear Nrf2 accumulation and ARE-binding activity. Moreover, silencing Nrf2 markedly reduced ARE-driven activity induced by EDYGA. Docking results proved that glutamate residues of peptide EDYGA directly bind to Arg 415 of Kelch domain receptor pocke. The results were helpful in understanding the antioxidant activity of peptides from soft-shelled turtle which have potential to be used in foods and drugs as functional ingredients. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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