Seventeen novel angiotensin converting enzyme (ACE) inhibitory peptides from the protein hydrolysate of<i>Mytilus edulis</i>: isolation, identification, molecular docking study, and protective function on HUVECs

Suo, Shi-Kun; Zhao, Yu-Qin; Wang, Yumei; Pan, Xiao-yang; Chi, Chang-Feng; Wang, Bin

doi:10.1039/d2fo00275b

Cited by 45 publications

(49 citation statements)

References 67 publications

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“…The binding sites of Keap1 in the Kelch domain can be divided into five sub-pockets, namely P1 (Arg415, Ile461, Gly462, Phe478, Arg483 and Ser508), P2 (Ser363, Arg380, Asn382 and Asn414), P3 (Gly509, Ser555, Ala556, Gly571, Ser602 and Gly603), P4 (Tyr525, Gln530 and Tyr572), and P5 (Tyr334 and Phe577) [ 45 , 46 ]. Bioactive peptides bind to other macromolecular substances mainly through hydrogen bond force, van der Waals force and electrostatic interaction force, among which hydrogen bond force is the most important [ 27 , 47 ]. The molecular docking analysis indicated that the affinity of TCP3 with the middle cavity and bottom of Kelch domain was −7.4 kcal/mol and −6.6 kcal/mol, which was similar to those of TCP6 (−8.9 kcal/mol) and TCP9 (−8.5 kcal/mol) interacted with the middle cavity of Kelch domain.…”

Section: Resultsmentioning

confidence: 99%

Bioactive Peptides from Skipjack Tuna Cardiac Arterial Bulbs (II): Protective Function on UVB-Irradiated HaCaT Cells through Antioxidant and Anti-Apoptotic Mechanisms

Kong

Cai

et al. 2023

Marine Drugs

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The aim of this study was to investigate the protective function and mechanism of TCP3 (PKK), TCP6 (YEGGD) and TCP9 (GPGLM) from skipjack tuna cardiac arterial bulbs on skin photoaging using UVB-irradiated HaCaT cell model. The present results indicated that TCP3 (PKK), TCP6 (YEGGD) and TCP9 (GPGLM) had significant cytoprotective effect on UVB-irradiated HaCaT cells (p < 0.001). Hoechst 33342 staining showed that apoptosis of UV-irradiated HaCaT cells could be significantly reduced by the treatment of TCP3 (PKK), TCP6 (YEGGD) and TCP9 (GPGLM); JC-1 staining showed that TCP3 (PKK), TCP6 (YEGGD) and TCP9 (GPGLM) could protect HaCaT cells from apoptosis by restoring mitochondrial membrane potential (MMP); Furthermore, TCP3 (PKK), TCP6 (YEGGD) and TCP9 (GPGLM) could significantly down-regulate the ratio of Bax/Bcl-2 and reduce the expression level of the apoptosis-executing protein Caspase-3 by decreasing the expression of protein Caspase-8 and Caspase-9 (p < 0.05). The action mechanism indicated that TCP3 (PKK), TCP6 (YEGGD) and TCP9 (GPGLM) could up-regulate the expression levels of Nrf2, NQO1 and HO-1 (p < 0.05), which further increased the activity of downstream proteases (SOD, CAT and GSH-Px), and scavenged reactive oxygen species (ROS) and decreased the intracellular levels of malondialdehyde (MDA). In addition, molecular docking indicated that TCP3 (PKK) and TCP6 (YEGGD) could competitively inhibit the Nrf2 binding site because they can occupy the connection site of Nrf2 by binding to the Kelch domain of Keap1 protein. TCP9 (GPGLM) was inferred to be non-competitive inhibition because it could not bind to the active site of the Kelch domain of Keap1 protein. In summary, the antioxidant peptides TCP3 (PKK), TCP6 (YEGGD) and TCP9 (GPGLM) from cardiac arterial bulbs of skipjack tuna can effectively protect HaCaT cells from UVB-irradiated damage and can be used in the development of healthy and cosmetic products to treat diseases caused by UV radiation.

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Section: Resultsmentioning

confidence: 99%

Bioactive Peptides from Skipjack Tuna Cardiac Arterial Bulbs (II): Protective Function on UVB-Irradiated HaCaT Cells through Antioxidant and Anti-Apoptotic Mechanisms

Kong

Cai

et al. 2023

Marine Drugs

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“…Protein hydrolysates are complex mixtures of peptides with different molecular size and amino acid composition, which are the most critical factors affecting the separating and purifying process of BPs [ 4 , 20 ]. Therefore, ultrafiltration technology usually acts as a powerful technique to enrich APs with small MWs from various hydrolysates [ 21 , 55 ].…”

Section: Discussionmentioning

confidence: 99%

“…The findings were consistent with the results in existing literature that small MW AP fractions of protein hydrolysates from different marine resources, such as bluefin leatherjacket skins [ 19 ], monkfish muscle [ 21 ], blue mussel [ 45 ], skate cartilages [ 55 ], Antarctic krill [ 50 ], and tuna milts [ 33 ] and heads [ 39 ], had the strongest radical scavenging abilities. In addition, chromatographic methods, including ion exchange chromatography, gel permeation chromatography, and RP-HPLC, are generally applied to purify peptides from hydrolysate fractions depending on their acidity/basicity, molecular size, and adsorption affinities [ 1 , 4 ]. On these methods, 11 antioxidant peptides (TCP1–TCP11) were purified from protein hydrolysate of tuna cardiac arterial bulbs and presented significant antioxidant activity.…”

Section: Discussionmentioning

confidence: 99%

“…Bioactive peptides (BPs) are usually composed of 2–20 amino acid (AA) residues and generated from plant, animal, and microorganism proteins by chemical degradation, biological fermentation, and enzymatic hydrolysis methods [ 1 , 2 , 3 , 4 ]. Beyond their well-recognized nutritional value, BPs have been turned out to be of great value in advancing human health because of their significant biological activities including anticancer [ 5 , 6 ], antioxidant [ 7 ], antihypertensive [ 8 , 9 ], antiinflammatory [ 10 ], hypolipidemic [ 11 ], immunoreglatory [ 6 ], anti-diabetic [ 12 ], and mineral binding activities [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

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Bioactive Peptides from Skipjack Tuna Cardiac Arterial Bulbs: Preparation, Identification, Antioxidant Activity, and Stability against Thermal, pH, and Simulated Gastrointestinal Digestion Treatments

Cai

Wang

et al. 2022

Marine Drugs

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Cardiac arterial bulbs of Skipjack tuna (Katsuwonus pelamis) are rich in elastin, and its hydrolysates are high quality raw materials for daily cosmetics. In order to effectively utilizing Skipjack tuna processing byproducts-cardiac arterial bulbs and to prepare peptides with high antioxidant activity, pepsin was selected from six proteases for hydrolyzing proteins, and the best hydrolysis conditions of pepsin were optimized. Using ultrafiltration and chromatographic methods, eleven antioxidant peptides were purified from protein hydrolysate of tuna cardiac arterial bulbs. Four tripeptides (QGD, PKK, GPQ and GLN) were identified as well as seven pentapeptides (GEQSN, GEEGD, YEGGD, GEGER, GEGQR, GPGLM and GDRGD). Three out of them, namely the tripeptide PKK and the pentapeptides YEGGD and GPGLM exhibited the highest radical scavenging activities on 2,2-diphenyl-1-picrylhydrazyl (DPPH), hydroxyl, 2,2’-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) and superoxide anion assays. They also showed to protect plasmid DNA and HepG2 cells against H2O2-induced oxidative stress. Furthermore, they exhibited high stability under temperature ranged from 20-100 °C, pH values ranged from 3-11, and they simulated gastrointestinal digestion for 240 min. These results suggest that the prepared eleven antioxidant peptides from cardiac arterial bulbs, especially the three peptides PKK, YEGGD, and GPGLM, could serve as promising candidates in health-promoting products due to their high antioxidant activity and their stability.

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“…Moreover, ICY, LSFR, and IYSP could positively influence the production of nitric oxide (NO) and endothelin-(ET-) secretion in human umbilical vein endothelial cells (HUVECs) and weaken the adverse impact of norepinephrine (NE) on the production of NO and ET-. In addition, ICY, LSFR, and IYSP could provide significant protection to HUVECs against H O damage by increasing antioxidase levels to decrease Introduction Hypertension, also known as high blood pressure, is the most critical factor influencing the morbidity and mortality of cardiovascular disease (CVD) and renal disease (1)(2)(3). The prevalence of hypertension is about 1.3 billion, and this population may grow to 1.56 billion by 2030, which will cause a global economic burden of $274 billion (4).…”

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confidence: 99%

Novel angiotensin-converting enzyme inhibitory peptides from tuna byproducts—milts: Preparation, characterization, molecular docking study, and antioxidant function on H2O2-damaged human umbilical vein endothelial cells

et al. 2022

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To prepare peptides with high angiotensin-converting enzyme (ACE) inhibitory (ACEi) activity, Alcalase was screened from five proteases and employed to prepare protein hydrolysate (TMH) of skipjack tuna (Katsuwonus pelamis) milts. Subsequently, 10 novel ACEi peptides were isolated from the high-ACEi activity TMH and identified as Tyr-Asp-Asp (YDD), Thr-Arg-Glu (TRE), Arg-Asp-Tyr (RDY), Thr-Glu-Arg-Met (TERM), Asp-Arg-Arg-Tyr-Gly (DRRYG), Ile-Cys-Tyr (ICY), Leu-Ser-Phe-Arg (LSFR), Gly-Val-Arg-Phe (GVRF), Lys-Leu-Tyr-Ala-Leu-Phe (KLYALF), and Ile-Tyr-Ser-Pro (IYSP) with molecular weights of 411.35, 404.41, 452.45, 535.60, 665.69, 397.48, 521.61, 477.55, 753.91, and 478.53 Da, respectively. Among them, the IC50 values of ICY, LSFR, and IYSP on ACE were 0.48, 0.59, and 0.76 mg/mL, respectively. The significant ACEi activity of ICY, LSFR, and IYSP with affinities of −7.0, −8.5, and −8.3 kcal/mol mainly attributed to effectively combining with the ACEi active sites through hydrogen bonding, electrostatic force, and hydrophobic interaction. Moreover, ICY, LSFR, and IYSP could positively influence the production of nitric oxide (NO) and endothelin-1 (ET-1) secretion in human umbilical vein endothelial cells (HUVECs) and weaken the adverse impact of norepinephrine (NE) on the production of NO and ET-1. In addition, ICY, LSFR, and IYSP could provide significant protection to HUVECs against H2O2 damage by increasing antioxidase levels to decrease the contents of reactive oxide species and malondialdehyde. Therefore, the ACEi peptides of ICY, LSFR, and IYSP are beneficial functional molecules for healthy foods against hypertension and cardiovascular diseases.

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Seventeen novel angiotensin converting enzyme (ACE) inhibitory peptides from the protein hydrolysate ofMytilus edulis: isolation, identification, molecular docking study, and protective function on HUVECs

Abstract: In the study, seventeen angiotensin converting enzyme (ACE) inhibitory peptides were isolated from protein hydrolysate of blue mussel (Mytilus edulis) and identified as MFR, MFV, FV, KP, QP, QVK, IK,...

Cited by 45 publications

References 67 publications

Bioactive Peptides from Skipjack Tuna Cardiac Arterial Bulbs (II): Protective Function on UVB-Irradiated HaCaT Cells through Antioxidant and Anti-Apoptotic Mechanisms

Bioactive Peptides from Skipjack Tuna Cardiac Arterial Bulbs (II): Protective Function on UVB-Irradiated HaCaT Cells through Antioxidant and Anti-Apoptotic Mechanisms

Bioactive Peptides from Skipjack Tuna Cardiac Arterial Bulbs: Preparation, Identification, Antioxidant Activity, and Stability against Thermal, pH, and Simulated Gastrointestinal Digestion Treatments

Novel angiotensin-converting enzyme inhibitory peptides from tuna byproducts—milts: Preparation, characterization, molecular docking study, and antioxidant function on H2O2-damaged human umbilical vein endothelial cells

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