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Current Pharmaceutical Design

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ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Research Article

Bioactive Peptides Originating from Gastrointestinal Endogenous Proteins in the Growing Pig: In Vivo Identification

Author(s): Lakshmi A. Dave, Maria Hayes, Leticia Mora, Shane M. Rutherfurd, Carlos A. Montoya and Paul J. Moughan*

Volume 27, Issue 11, 2021

Published on: 07 December, 2020

Page: [1382 - 1395] Pages: 14

DOI: 10.2174/1381612826666201207111209

Price: $65

Abstract

Background: Recent in silico and in vitro studies have shown that gastrointestinal endogenous proteins (GEP) are a source of bioactive peptides. To date, however, the presence of such peptides in the lumen of the digestive tract has not been demonstrated.

Objective: We investigated the generation of GEP-derived bioactive peptides in the growing pig fed a proteinfree diet.

Methods: Stomach chyme (SC) and jejunal digesta (JD) fractions from 6 growing pigs (two sampling times) were assessed for their angiotensin-I-converting enzyme (ACE-I; EC 3.4.15.1) inhibition, and antioxidant activity using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) inhibition, ferric reducing antioxidant power (FRAP) and microsomal lipid peroxidation (MLP) inhibition assays.

Results: Two of the fractions prepared from JD samples inhibited ACE-I and DPPH by 81 (± 2.80)% and 94 (±0.66)%. SC fractions were found to inhibit MLP between 15-39 (±3.52-1.40)%. The study identified over 180 novel peptide sequences that were related to the determined bioactivities, including a porcine serum albuminderived peptide (FAKTCVADESAENCDKS), corresponding to f(7-23) of the human serum albumin peptide LVNEVTEFAKTCVADESAENCDKSLHTLF that was previously identified from the digests of the latter GEP.

Conclusion: This study provides the first in vivo evidence for GEP as a source of bioactive peptides. These new findings help advance our knowledge of the latent bioactive role of GEP-derived peptides in mammalian nutrition and health and their potential pharmaceutical applications.

Keywords: Angiotensin-I converting enzyme (ACE-I) inhibition, antioxidant peptides, exogenous bioactive peptides, ferric reducing antioxidant power, gut non-dietary proteins, microsomal lipid peroxidation inhibition, non-dietary proteins, porcine model, serum albumin.

[1]
Moughan PJ, Rutherfurd SM, Montoya CA, Dave LA. Food-derived bioactive peptides--a new paradigm. Nutr Res Rev 2014; 27(1): 16-20.
[http://dx.doi.org/10.1017/S0954422413000206] [PMID: 24231033]
[2]
Moughan PJ, Rutherfurd SM. Gut luminal endogenous protein: implications for the determination of ileal amino acid digestibility in humans. Br J Nutr 2012; 108(Suppl. 2): S258-63.
[http://dx.doi.org/10.1017/S0007114512002474] [PMID: 23107536]
[3]
Gaudichon C, Bos C, Morens C, et al. Ileal losses of nitrogen and amino acids in humans and their importance to the assessment of amino acid requirements. Gastroenterology 2002; 123(1): 50-9.
[http://dx.doi.org/10.1053/gast.2002.34233] [PMID: 12105833]
[4]
Dietary protein quality evaluation in human nutrition FAO Food and Nutrition Paper Report of an FAO Expert Consultation 2013.
[5]
Souffrant WB, Rérat A, Laplace JP, et al. Exogenous and endogenous contributions to nitrogen fluxes in the digestive tract of pigs fed a casein diet. III. Recycling of endogenous nitrogen. Reprod Nutr Dev 1993; 33(4): 373-82.
[http://dx.doi.org/10.1051/rnd:19930406] [PMID: 8240681]
[6]
Souffrant WB, Rérat A, Laplace JP, et al. Report of an FAO Expert Consultation. Dietary protein quality evaluation in human nutrition UNFAO
[http://dx.doi.org/10.1051/rnd:19930406] [PMID: 8240681]
[7]
Snook JT, Meyer JH. Response of digestive enzymes to dietary protein. J Nutr 1964; 82(4): 409-14.
[http://dx.doi.org/10.1093/jn/82.4.409] [PMID: 14151125]
[8]
Van Der Schoor SRD, Reeds PJ, Stoll B, et al. The high metabolic cost of a functional gut. Gastroenterology 2002; 123(6): 1931-40.
[http://dx.doi.org/10.1053/gast.2002.37062] [PMID: 12454850]
[9]
Dave LA, Montoya CA, Rutherfurd SM, Moughan PJ. Gastrointestinal endogenous proteins as a source of bioactive peptides--an in silico study. PLoS One 2014; 9(6)e98922
[http://dx.doi.org/10.1371/journal.pone.0098922] [PMID: 24901416]
[10]
Dave LA, Hayes M, Rutherfurd SM, Moughan PJ. Novel dipeptidyl peptidase IV inhibitory and antioxidant peptides derived from human gastrointestinal endogenous proteins. Int J Pept Res Ther 2016; 22(3): 355-69.
[http://dx.doi.org/10.1007/s10989-016-9515-y]
[11]
Dave LA, Hayes M, Mora L, Montoya CA, Moughan PJ, Rutherfurd SM. Gastrointestinal endogenous protein-derived bioactive peptides: An in vitro study of their gut modulatory potential. Int J Mol Sci 2016; 17(4): 482.
[http://dx.doi.org/10.3390/ijms17040482] [PMID: 27043546]
[12]
Dave LA, Hayes M, Montoya CA, Rutherfurd SM, Moughan PJ. Human gut endogenous proteins as a potential source of angiotensin-I-converting enzyme (ACE-I)-, renin inhibitory and antioxidant peptides. Peptides 2015; 76: 30-44.
[PMID: 26617077]
[13]
Shahidi F, Zhong Y. Bioactive peptides. J AOAC Int 2008; 91(4): 914-31.
[http://dx.doi.org/10.1093/jaoac/91.4.914] [PMID: 18727554]
[14]
Fändriks L. The renin-angiotensin system and the gastrointestinal mucosa. Acta Physiol (Oxf) 2011; 201(1): 157-67.
[http://dx.doi.org/10.1111/j.1748-1716.2010.02165.x] [PMID: 20626369]
[15]
Kvietys PR. Postprandial hyperemiathe gastrointestinal circulation. San Rafael, CA: Morgan & Claypool Life Sciences 2010.
[16]
Wegman-Ostrosky T, Soto-Reyes E, Vidal-Millán S, Sánchez-Corona J. The renin-angiotensin system meets the hallmarks of cancer. J Renin Angiotensin Aldosterone Syst 2013; 16(2): 227-33.
[PMID: 23934336]
[17]
Circu ML, Aw TY. Redox biology of the intestine. Free Radic Res 2011; 45(11-12): 1245-66.
[http://dx.doi.org/10.3109/10715762.2011.611509] [PMID: 21831010]
[18]
Circu ML, Aw TY. Intestinal redox biology and oxidative stress. Semin Cell Dev Biol 2012; 23(7): 729-37.
[http://dx.doi.org/10.1016/j.semcdb.2012.03.014] [PMID: 22484611]
[19]
Halliwell B, Zhao K, Whiteman M. The gastrointestinal tract: a major site of antioxidant action? Free Radic Res 2000; 33(6): 819-30.
[http://dx.doi.org/10.1080/10715760000301341] [PMID: 11237104]
[20]
Atashgahi S, Shetty SA, Smidt H, de Vos WM. Flux, impact, and fate of halogenated xenobiotic compounds in the gut. Front Physiol 2018; 9: 888-.
[http://dx.doi.org/10.3389/fphys.2018.00888] [PMID: 30042695]
[21]
Halliwell B. Antioxidants in human health and disease. Annu Rev Nutr 1996; 16: 33-50.
[http://dx.doi.org/10.1146/annurev.nu.16.070196.000341] [PMID: 8839918]
[22]
Montoya CA, Rutherfurd SM, Olson TD, et al. Actinidin from kiwifruit (Actinidia deliciosa cv. Hayward) increases the digestion and rate of gastric emptying of meat proteins in the growing pig. Br J Nutr 2014; 111(6): 957-67.
[http://dx.doi.org/10.1017/S0007114513003401] [PMID: 24252432]
[23]
Montoya CA, Cabrera DL, Zou M, Boland MJ, Moughan PJ. The rate at which digested protein enters the small intestine modulates the rate of amino acid digestibility throughout the small intestine of growing pigs. J Nutr 2018; 148(11): 1743-50.
[http://dx.doi.org/10.1093/jn/nxy193] [PMID: 30383281]
[24]
Rutherfurd SM, Montoya CA, Zou ML, Moughan PJ, Drummond LN, Boland MJ. Effect of actinidin from kiwifruit (Actinidia deliciosa cv. Hayward) on the digestion of food proteins determined in the growing rat. Food Chem 2011; 129(4): 1681-9.
[http://dx.doi.org/10.1016/j.foodchem.2011.06.031]
[25]
Fitzgerald C, Mora-Soler L, Gallagher E, et al. Isolation and characterization of bioactive pro-peptides with in vitro renin inhibitory activities from the macroalga Palmaria palmata. J Agric Food Chem 2012; 60(30): 7421-7.
[http://dx.doi.org/10.1021/jf301361c] [PMID: 22747312]
[26]
Benzie IF, Strain JJ. The ferric reducing ability of plasma (FRAP) as a measure of “antioxidant power”: the FRAP assay. Anal Biochem 1996; 239(1): 70-6.
[http://dx.doi.org/10.1006/abio.1996.0292] [PMID: 8660627]
[27]
Bolanos de la Torre AA, Henderson T, Nigam PS, Owusu-Apenten RK. A universally calibrated microplate ferric reducing antioxidant power (FRAP) assay for foods and applications to Manuka honey. Food Chem 2015; 174: 119-23.
[http://dx.doi.org/10.1016/j.foodchem.2014.11.009] [PMID: 25529660]
[28]
Nicklisch SCT, Waite JH. Optimized DPPH assay in a detergent-based buffer system for measuring antioxidant activity of proteins. MethodsX 2014; 1: 233-8.
[http://dx.doi.org/10.1016/j.mex.2014.10.004] [PMID: 25530949]
[29]
Goupy P, Dufour C, Loonis M, Dangles O. Quantitative kinetic analysis of hydrogen transfer reactions from dietary polyphenols to the DPPH radical. J Agric Food Chem 2003; 51(3): 615-22.
[http://dx.doi.org/10.1021/jf025938l] [PMID: 12537431]
[30]
van der Sluis AA, Dekker M, Verkerk R, Jongen WM. An improved, rapid in vitro method to measure antioxidant activity. Application on selected flavonoids and apple juice. J Agric Food Chem 2000; 48(9): 4116-22.
[http://dx.doi.org/10.1021/jf000156i] [PMID: 10995324]
[31]
Mora L, Gallego M, Aristoy MC, Fraser PD, Toldrá F. Peptides naturally generated from ubiquitin-60S ribosomal protein as potential biomarkers of dry-cured ham processing time. Food Control 2015; 48: 102-7.
[http://dx.doi.org/10.1016/j.foodcont.2013.12.029]
[32]
Kedare SB, Singh RP. Genesis and development of DPPH method of antioxidant assay. J Food Sci Technol 2011; 48(4): 412-22.
[http://dx.doi.org/10.1007/s13197-011-0251-1] [PMID: 23572765]
[33]
Udenigwe CC, Aluko RE. Chemometric analysis of the amino acid requirements of antioxidant food protein hydrolysates. Int J Mol Sci 2011; 12(5): 3148-61.
[http://dx.doi.org/10.3390/ijms12053148] [PMID: 21686175]
[34]
Minkiewicz P, Dziuba J, Iwaniak A, Dziuba M, Darewicz M. BIOPEP database and other programs for processing bioactive peptide sequences. J AOAC Int 2008; 91(4): 965-80.
[http://dx.doi.org/10.1093/jaoac/91.4.965] [PMID: 18727559]
[35]
Human protein atlas. 2015. Available from: http://www.proteinatlas.org/
[36]
Gremel G, Wanders A, Cedernaes J, et al. The human gastrointestinal tract-specific transcriptome and proteome as defined by RNA sequencing and antibody-based profiling. J Gastroenterol 2015; 50(1): 46-57.
[http://dx.doi.org/10.1007/s00535-014-0958-7] [PMID: 24789573]
[37]
Uhlén M, Fagerberg L, Hallström BM, et al. Proteomics. Tissue-based map of the human proteome. Science 2015; 347(6220)1260419
[http://dx.doi.org/10.1126/science.1260419] [PMID: 25613900]
[38]
Trompette A, Claustre J, Caillon F, Jourdan G, Chayvialle JA, Plaisancié P. Milk bioactive peptides and β-casomorphins induce mucus release in rat jejunum. J Nutr 2003; 133(11): 3499-503.
[http://dx.doi.org/10.1093/jn/133.11.3499] [PMID: 14608064]
[39]
Bauchart C, Morzel M, Chambon C, et al. Peptides reproducibly released by in vivo digestion of beef meat and trout flesh in pigs. Br J Nutr 2007; 98(6): 1187-95.
[http://dx.doi.org/10.1017/S0007114507761810] [PMID: 17764598]
[40]
Boutrou R, Gaudichon C, Dupont D, et al. Sequential release of milk protein-derived bioactive peptides in the jejunum in healthy humans. Am J Clin Nutr 2013; 97(6): 1314-23.
[http://dx.doi.org/10.3945/ajcn.112.055202] [PMID: 23576048]
[41]
Boutrou R, Henry G, Sanchez-Rivera L. On the trail of milk bioactive peptides in human and animal intestinal tracts during digestion: A review. Dairy Sci Technol 2015; 95(6)
[http://dx.doi.org/10.1007/s13594-015-0210-0]
[42]
Moughan PJ, Souffrant WB, Hodgkinson SM. Physiological approaches to determining gut endogenous amino acid flows in the mammal. Arch Tierernahr 1998; 51(2-3): 237-52.
[http://dx.doi.org/10.1080/17450399809381922] [PMID: 9672720]
[43]
Deglaire A, Bos C, Tomé D, Moughan PJ. Ileal digestibility of dietary protein in the growing pig and adult human. Br J Nutr 2009; 102(12): 1752-9.
[http://dx.doi.org/10.1017/S0007114509991267] [PMID: 19706206]
[44]
Jackson AA. Nitrogen trafficking and recycling through the human bowel. Nestle Nutr Workshop Ser Clin Perform Programme 2000; 3: 89-105.
[http://dx.doi.org/10.1159/000061801] [PMID: 11490615]
[45]
Miner-Williams W, Deglaire A, Benamouzig R, Fuller MF, Tomé D, Moughan PJ. Endogenous proteins in terminal ileal digesta of adult subjects fed a casein-based diet. Am J Clin Nutr 2012; 96(3): 508-15.
[http://dx.doi.org/10.3945/ajcn.111.033472] [PMID: 22836032]
[46]
Guo L, Harnedy PA, Zhang L, et al. In vitro assessment of the multifunctional bioactive potential of Alaska pollock skin collagen following simulated gastrointestinal digestion. J Sci Food Agric 2015; 95(7): 1514-20.
[http://dx.doi.org/10.1002/jsfa.6854] [PMID: 25082083]
[47]
Harnedy PA, FitzGerald RJ. In vitro assessment of the cardioprotective, anti-diabetic and antioxidant potential of Palmaria palmata protein hydrolysates. J Appl Phycol 2013; 25(6): 1793-803.
[http://dx.doi.org/10.1007/s10811-013-0017-4]
[48]
Yousr M, Howell N. Antioxidant and ACE inhibitory bioactive peptides purified from egg yolk proteins. Int J Mol Sci 2015; 16(12): 29161-78.
[http://dx.doi.org/10.3390/ijms161226155] [PMID: 26690134]
[49]
Siow H-L, Gan C-Y. Extraction, identification, and structure–activity relationship of antioxidative and α-amylase inhibitory peptides from cumin seeds (Cuminum cyminum). J Funct Foods 2016; 22: 1-12.
[http://dx.doi.org/10.1016/j.jff.2016.01.011]
[50]
Esteve C, Marina ML, García MC. Novel strategy for the revalorization of olive (Olea europaea) residues based on the extraction of bioactive peptides. Food Chem 2015; 167: 272-80.
[http://dx.doi.org/10.1016/j.foodchem.2014.06.090] [PMID: 25148989]
[51]
Di Bernardini R, Mullen AM, Bolton D, Kerry J, O’Neill E, Hayes M. Assessment of the angiotensin-I-converting enzyme (ACE-I) inhibitory and antioxidant activities of hydrolysates of bovine brisket sarcoplasmic proteins produced by papain and characterisation of associated bioactive peptidic fractions. Meat Sci 2012; 90(1): 226-35.
[http://dx.doi.org/10.1016/j.meatsci.2011.07.008] [PMID: 21880436]
[52]
Meira SMM, Daroit DJ, Helfer VE, et al. Bioactive peptides in water-soluble extracts of ovine cheeses from Southern Brazil and Uruguay. Food Res Int 2012; 48(1): 322-9.
[http://dx.doi.org/10.1016/j.foodres.2012.05.009]
[53]
Miner-Williams W, Moughan PJ, Fuller MF. Endogenous components of digesta protein from the terminal ileum of pigs fed a casein-based diet. J Agric Food Chem 2009; 57(5): 2072-8.
[http://dx.doi.org/10.1021/jf8023886] [PMID: 19203191]
[54]
Brassinne A. Gastric clearance of serum albumin in normal man and in certain gastroduodenal disorders. Gut 1974; 15(3): 194-9.
[http://dx.doi.org/10.1136/gut.15.3.194] [PMID: 4210183]
[55]
Glass GBJ, Ishimori A. Passage of serum albumin into the stomach. Its detection by paper electrophoresis of gastric juice in protein-losing gastropathies and gastric cancer. Am J Dig Dis 1961; 6(2): 103-33.
[http://dx.doi.org/10.1007/BF02231798] [PMID: 13705938]
[56]
Bennick A. Salivary proline-rich proteins. Mol Cell Biochem 1982; 45(2): 83-99.
[http://dx.doi.org/10.1007/BF00223503] [PMID: 6810092]
[57]
Vitali A. Proline-rich peptides: multifunctional bioactive molecules as new potential therapeutic drugs. Curr Protein Pept Sci 2015; 16(2): 147-62.
[http://dx.doi.org/10.2174/1389203716666150102110817] [PMID: 25692951]
[58]
Foltz M, Meynen EE, Bianco V, van Platerink C, Koning TMMG, Kloek J. Angiotensin converting enzyme inhibitory peptides from a lactotripeptide-enriched milk beverage are absorbed intact into the circulation. J Nutr 2007; 137(4): 953-8.
[http://dx.doi.org/10.1093/jn/137.4.953] [PMID: 17374660]
[59]
[60]
Chruszcz M, Mikolajczak K, Mank N, Majorek KA, Porebski PJ, Minor W. Serum albumins-unusual allergens. Biochim Biophys Acta 2013; 1830(12): 5375-81.
[http://dx.doi.org/10.1016/j.bbagen.2013.06.016] [PMID: 23811341]
[61]
Nongonierma AB, FitzGerald RJ. The scientific evidence for the role of milk protein-derived bioactive peptides in humans: A Review. J Funct Foods 2015; 17: 640-56.
[http://dx.doi.org/10.1016/j.jff.2015.06.021]
[62]
Minkiewicz P, Darewicz M, Iwaniak A, et al. Common amino acid subsequences in a universal proteome - Relevance for food science. Int J Mol Sci 2015; 16(9): 20748-73.
[http://dx.doi.org/10.3390/ijms160920748] [PMID: 26340620]
[63]
Pluske JR, Turpin DL, Kim J-C. Gastrointestinal tract (gut) health in the young pig. Anim Nutr 2018; 4(2): 187-96.
[http://dx.doi.org/10.1016/j.aninu.2017.12.004] [PMID: 30140758]
[64]
Franzosa EA, Huang K, Meadow JF, et al. Identifying personal microbiomes using metagenomic codes. Proc Natl Acad Sci USA 2015; 112(22): E2930-8.
[http://dx.doi.org/10.1073/pnas.1423854112] [PMID: 25964341]
[65]
Rodríguez JM, Murphy K, Stanton C, et al. The composition of the gut microbiota throughout life, with an emphasis on early life. Microb Ecol Health Dis 2015; 26: 26050.
[PMID: 25651996]
[66]
Booijink CC, El-Aidy S, Rajilić-Stojanović M, et al. High temporal and inter-individual variation detected in the human ileal microbiota. Environ Microbiol 2010; 12(12): 3213-27.
[http://dx.doi.org/10.1111/j.1462-2920.2010.02294.x] [PMID: 20626454]
[67]
Nutrient requirements of swine. N.A.o In: National Research Council Council SNR, Ed Washington, DC: National Academy of Sciences. 1998.

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