ORIGINAL PAPER
Active sites of peptide from Arg-Ser-Ser protect against oxidative stress in HepG2 cells
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1
Guangdong Provincial Key Laboratory of Lingnan Specialty Food Science and Technology, Guangzhou, Guangdong, China
2
College of Light Industry and Food, Zhongkai University of Agriculture and Engineering, Guangzhou, Guangdong 510225, China
Submission date: 2021-10-24
Final revision date: 2021-11-16
Acceptance date: 2021-11-16
Online publication date: 2021-12-11
Publication date: 2021-12-20
Corresponding author
Huifan Liu
College of Light Industry and Food, Zhongkai University of Agriculture and Engineering, China
eFood 2021;2(4):193-200
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ABSTRACT
Peptide Arg-Ser-Ser (RSS) was derived from Lactobacillus amylolyticus co-incubated with edible Dendrobium aphyllum. Here, we further examined the antioxidative effects of RSS in HepG2 cells subjected to 2,2-azobis(2-methylpropanimidamidine) dihydrochloride-induced oxidative stress. RSS protected cells by eliminating the level of reactive oxygen species (ROS). The protein expression of antioxidant enzymes, Nrf2 and Keap1 determined by western blot, indicated that RSS might maintain cellular homeostasis by directly scavenging free radicals instead of by enzymatic system. Furthermore, quantum chemistry calculations and a characterization of electronic-related properties showed that the highest occupied molecular orbital energy distribution was on arginine residue. Pre-treatment with RSS with the active site methylated resulted in increased ROS levels, thereby verifying that N2-H3 is the active site for antioxidant activity. Our findings provide valuable insights into the antioxidant activity of RSS and a basis for developing antioxidant functional foods.
REFERENCES (32)
1.
Lin S, Jin Y, Liu M, Yang Y, Zhang M, Guo Y, et al. Research on the preparation of antioxidant peptides derived from egg white with assisting of high-intensity pulsed electric field. Food Chem 2013; 139: 300-306.
https://doi.org/10.1016/j.food....
2.
Sila A, Bougatef A. Antioxidant peptides from marine by-products: Isolation, identification and application in food systems. A review. J Funct Foods 2016; 21: 10-26.
https://doi.org/10.1016/j.jff.....
3.
Liu H, Ma J, Yin Z, Wu H. Characteristic Analysis of Peptide Fraction Extracted from Dendrobium aphyllum After In Vitro Gastrointestinal Digestion and Fermentation by Human Fecal Microbiota. Int J Pept Res Ther 2018; 1-10.
https://doi.org/10.1007/s10989....
4.
Tsai H J, Shang H F, Yeh C L, Yeh S L. Effects of arginine supplementation on antioxidant enzyme activity and macrophage response in burned mice. Burns 2002; 28: 258-263.
https://doi.org/10.1016/S0305-....
5.
Akhtar M J, Ahamed M, Alhadlaq H A, Alshamsan A. Mechanism of ROS scavenging and antioxidant signalling by redox metallic and fullerene nanomaterials: Potential implications in ROS associated degenerative disorders. Biochim Biophys Acta 2017; 1861: 802-813.
https://doi.org/10.1016/j.bbag....
6.
Ganesan B, Anandan R, Lakshmanan P T. Studies on the protective effects of betaine against oxidative damage during experimentally induced restraint stress in Wistar albino rats. Cell Stress Charperon 2011; 16: 641-652.
https://doi.org/10.1007/s12192....
7.
Liu H, Ye H, Sun C, Xi H, Ma J, Lai F, et al. Antioxidant activity in HepG2 cells, immunomodulatory effects in RAW 264.7 cells and absorption characteristics in Caco‐2 cells of the peptide fraction isolated from Dendrobium aphyllum. Int. J. Food. Sci. Tech. 2018; 53: 2027-2036.
https://doi.org/10.1111/ijfs.1....
8.
WH L, Liu F, Liu J, Zhao Q L, Dong J. Preparation of Grape Seed Peptide and Study on Its Ability to Scavenge Free Radicals. Food Res Development 2019; 40: 132-138.
9.
Mengmeng Z, Hong Z, Huixian L, Furao L, Xiaofeng L. Antioxidant Mechanism of Betaine without Free Radical Scavenging Ability. J Agri Food Chem 2016; 64: 7921-7930.
https://doi.org/10.1021/acs.ja....
10.
Liao W, Ning Z, Chen L, Wei Q, Yuan E, Yang J, et al. Intracellular Antioxidant Detoxifying Effects of Diosmetin on 2,2-Azobis(2-amidinopropane) Dihydrochloride (AAPH)-Induced Oxidative Stress through Inhibition of Reactive Oxygen Species Generation. J Agri Food Chem 2014; 62: 8648-8654.
https://doi.org/10.1021/jf5023....
11.
Ali H M, Ali I H. Structure-antioxidant activity relationships, QSAR, DFT calculation, and mechanisms of flavones and flavonols. Med Chem Res 2019; 28: 2262-2269.
https://doi.org/10.1007/s00044....
12.
Chen Y, Xiao H, Zheng J, Liang G. Structure-thermodynamics-antioxidant activity relationships of selected natural phenolic acids and derivatives: an experimental and theoretical evaluation. Plos One 2015; 10: e0121276.
https://doi.org/10.1371/journa....
13.
Pardeshi S, Dhodapkar R, Kumar A. Quantum chemical density functional theory studies on the molecular structure and vibrational spectra of Gallic acid imprinted polymers. Spectrochim Acta A 2013; 116: 562-573.
https://doi.org/10.1016/j.saa.....
14.
Cheng Y, Luo F, Zeng Z, Li W, Xiao Z, Bu H, et al. DFT-based quantitative structure-activity relationship studies for antioxidant peptides. Struct Chem 2015; 26: 739-747.
https://doi.org/10.1007/s11224....
15.
Wu J, Huo J, Huang M, Zhao M, Luo X, Sun B G. Structural characterization of a tetrapeptide from Sesame flavor-type Baijiu and its preventive effects against AAPH-induced oxidative stress in HepG2 cells. J Agric Food Chem 2017; 65: 10495-10594.
https://doi.org/10.1021/acs.ja....
16.
Wu J, Sun B, Luo X, Zhao M, Zheng F, Sun J, et al. Cytoprotective effects of a tripeptide from Chinese Baijiu against AAPH-induced oxidative stress in HepG2 cells via Nrf2 signaling. RSC Adv 2018; 8: 10898-10906.
https://doi.org/10.1039/C8RA01....
17.
Nakase I, Niwa M, Takeuchi T, Sonomura K, Kawabata N, Koike Y, et al. Cellular Uptake of Arginine-Rich Peptides: Roles for Macropinocytosis and Actin Rearrangement. Mol Ther 2004; 10: 1011-1022.
https://doi.org/10.1016/j.ymth....
18.
Vazdar, Mario, Heyda, Jan, Mason, Philip, et al. Arginine "Magic": Guanidinium Like-Charge Ion Pairing from Aqueous Salts to Cell Penetrating Peptides. Acc Chem Res 2018; 51: 1455-1464.
https://doi.org/10.1021/acs.ac....
19.
Costa T R, Amstalden M K, Ribeiro D L, Menaldo D L, Sampaio S V. CR-LAAO causes genotoxic damage in HepG2 tumor cells by oxidative stress. Toxicology 2018; 404-405.
https://doi.org/10.1016/j.tox.....
20.
Wang L, Ding L, Yu Z, Zhang T, Ma S, Liu J. Intracellular ROS scavenging and antioxidant enzyme regulating capacities of corn gluten meal-derived antioxidant peptides in HepG2 cells. Food Res Int 2016; 90: 33-41.
https://doi.org/10.1016/j.food....
21.
Sha J y, Zhou Y d, Yang J y, Leng J, Li J h, Hu J n, et al. Maltol (3-Hydroxy-2-methyl-4-pyrone) Slows d-Galactose-Induced Brain Aging Process by Damping the Nrf2/HO-1-Mediated Oxidative Stress in Mice. J Agric Food Chem 2019; 67: 10342-10351.
https://doi.org/10.1021/acs.ja....
22.
Pan, Cheol-Ho, Farag, Mohamed, Osman, Samir, et al. Isolation of major phenolics from Launaea spinosa and their protective effect on HepG2 cells damaged with t-BHP. Pharm Biol 2016; 54: 536-541.
https://doi.org/10.3109/138802....
23.
Yang C S, Ho C T, Zhang J, Wan X, Zhang K, Lim J. Antioxidants: Differing Meanings in Food Science and Health Science. J Agric Food Chem 2018; 66: 3063-3068.
https://doi.org/10.1021/acs.ja....
24.
Yamamoto T, Suzuki T, Kobayashi A, Wakabayashi J, Maher J, Motohashi H, et al. Physiological Significance of Reactive Cysteine Residues of Keap1 in Determining Nrf2 Activity. Mol Cell Biol 2008; 28: 2758-2770.
https://doi.org/10.1128/MCB.01....
25.
Bartolotti L J, Edney E O. Investigation of the correlation between the energy of the highest occupied molecular orbital (HOMO) and the logarithm of the OH rate constant of hydrofluorocarbons and hydrofluoroethers. Int J Chem Kinet 1994; 26: 913-920.
https://doi.org/10.1002/kin.55....
26.
Thabo P, Olasunkanmi L O, Indra B, Adekunle A S, Kabanda M M, Ebenso E E. Adsorption and Corrosion Inhibition Studies of Some Selected Dyes as Corrosion Inhibitors for Mild Steel in Acidic Medium: Gravimetric, Electrochemical, Quantum Chemical Studies and Synergistic Effect with Iodide Ions. Molecules 2015; 20: 16004.
https://doi.org/10.3390/molecu....
27.
Alaşalvar C, Soylu M S, Güder A, Albayrak Ç, Apaydın G, Dilek N. Molecular structure, quantum mechanical calculation and radical scavenging activities of ( E )-4,6-dibromo-2-[(3,5-dimethylphenylimino)methyl]-3-methoxyphenol and ( E )-4,6-dibromo-2-[(2,6-dimethylphenylimino)methyl]-3-methoxyphenol compounds. Spectrochim Acta A Mol Biomol Spectrosc 2014; 130: 357-366.
https://doi.org/10.1016/j.saa.....
28.
Arunan E, Desiraju G, Klein R, Sadlej J, Scheiner S, Alkorta I, et al. Definition of the Hydrogen Bond (IUPAC Recommendations 2011). Pure Appl Chem 2011; 83: 1637-1641.
https://doi.org/10.1351/PAC-RE....
29.
Barzegar A, Davari M D, Chaparzadeh N, Zarghami N, Pedersen J Z, Incerpi S, et al. Theoretical and experimental studies on the structure-antioxidant activity relationship of synthetic 4-methylcoumarins. J Iran Chem Soc 2011; 8: 973-982.
https://doi.org/10.1007/BF0324....
30.
Avilés-Moreno J R, Berden G, Oomens J, Martínez-Haya B. Guanidinium/ammonium competition and proton transfer in the interaction of the amino acid arginine with the tetracarboxylic 18-crown-6 ionophore. Phys Chem Chem Phys 2018; 20: 4067.
https://doi.org/10.1039/C7CP07....
31.
Milyutina N P, Ananyan A A, Shchugalei V S. Antiradical and antioxidative effect of arginine and its influence on lipid peroxidation activity during hypoxia. B Exp Biol Med 1990; 110: 1198-1200.
https://doi.org/10.1007/BF0084....
32.
Kim G N, Jang H D. Protective Mechanism of Quercetin and Rutin Using Glutathione Metabolism on H(2)O(2)-induced Oxidative Stress in HepG2 Cells. Ann NY Acad Sci 2009; 1171: 530-537.
https://doi.org/10.1111/j.1749....