Binding of CML-Modified as Well as Heat-Glycated β-lactoglobulin to Receptors for AGEs Is Determined by Charge and Hydrophobicity
Abstract
:1. Introduction
2. Results
2.1. Chemical Modification and Glycation
2.2. Structural Changes
2.3. Receptor Binding
3. Discussion
4. Materials and Methods
4.1. Chemicals
4.2. CML Introduction in BLG
4.3. Glycation of β-lactoglobulin
4.4. Quantification of CML Using LC-MS/MS
4.5. Quantification of Free Available Amino Groups
4.6. Secondary Structure
4.7. Surface Hydrophobicity (ANS-Assay)
4.8. ThT-Assay
4.9. Native Gel Electrophoresis
4.10. Inhibition ELISA Assay for Receptor Binding
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
Abbreviations
AGEs | Advanced glycation end products |
ANS | 8-anilino-1-naphthalenesulfonic acid |
APCs | Antigen presenting cells |
BLG | β-lactoglobulin |
BSA | Bovine serum albumin |
CD | Circular dichroism |
CML | Nε-carboxymethyl lysine |
MR | Maillard reaction |
MRPs | Maillard reaction products |
NaCl | Sodium chloride |
OPA | o-phthaldialdehyde |
oxLDL | Oxidised low density lipoprotein |
PBS | Phosphate saline buffer |
RAGE | Receptor for advanced glycation end products |
sRAGE | Soluble form of RAGE |
ThT | Thioflavin T |
References
- Martorell-Aragonés, A.; Echeverría-Zudaire, L.; Alonso-Lebrero, E.; Boné-Calvo, J.; Martín-Muñoz, M.F.; Nevot-Falcó, S.; Piquer-Gibert, M.; Valdesoiro-Navarrete, L.; Food Allergy Committee of, S. Position document: IgE-mediated cow’s milk allergy. Allergol. Immunopathol. 2015, 43, 507–526. [Google Scholar] [CrossRef]
- Alexander, L.J.; Hayes, G.; Pearse, M.J.; Stewart, A.F.; Willis, I.M.; Mackinlay, A.G. Complete sequence of the bovine β-lactoglobulin cDNA. Nucleic Acids Res. 1989, 17, 6739. [Google Scholar] [CrossRef] [PubMed]
- Uribarri, J.; Cai, W.; Sandu, O.; Peppa, M.; Goldberg, T.; Vlassara, H. Diet-derived advanced glycation end products are major contributors to the body’s AGE pool and induce inflammation in healthy subjects. In Annals of the New York Academy of Sciences; New York Academy of Sciences: New York, NY, USA, 2005; Volume 1043, pp. 461–466. [Google Scholar]
- Smith, P.K.; Masilamani, M.; Li, X.M.; Sampson, H.A. The false alarm hypothesis: Food allergy is associated with high dietary advanced glycation end-products and proglycating dietary sugars that mimic alarmins. J. Allergy Clin. Immunol. 2017, 139, 429–437. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Di Pino, A.; Currenti, W.; Urbano, F.; Scicali, R.; Piro, S.; Purrello, F.; Rabuazzo, A.M. High intake of dietary advanced glycation end-products is associated with increased arterial stiffness and inflammation in subjects with type 2 diabetes. Nutr. Metab. Cardiovasc. Dis. 2017, 27, 978–984. [Google Scholar] [CrossRef] [PubMed]
- Uribarri, J.; del Castillo, M.D.; de la Maza, M.P.; Filip, R.; Gugliucci, A.; Luevano-Contreras, C.; Macías-Cervantes, M.H.; Markowicz Bastos, D.H.; Medrano, A.; Menini, T.; et al. Dietary advanced glycation end products and their role in health and disease. Adv. Nutr. 2015, 6, 461–473. [Google Scholar] [CrossRef] [PubMed]
- Peppa, M.; Uribarri, J.; Cai, W.; Lu, M.; Vlassara, H. Glycoxidation and Inflammation in Renal Failure Patients. Am. J. Kidney Dis. 2004, 43, 690–695. [Google Scholar] [CrossRef] [PubMed]
- Leung, C.; Herath, C.B.; Jia, Z.; Goodwin, M.; Mak, K.Y.; Watt, M.J.; Forbes, J.M.; Angus, P.W. Dietary glycotoxins exacerbate progression of experimental fatty liver disease. J. Hepatol. 2014, 60, 832–838. [Google Scholar] [CrossRef]
- Van Der Lugt, T.; Weseler, A.R.; Gebbink, W.A.; Vrolijk, M.F.; Opperhuizen, A.; Bast, A. Dietary advanced glycation endproducts induce an inflammatory response in human macrophages in vitro. Nutrients 2018, 10, 1868. [Google Scholar] [CrossRef] [Green Version]
- Hilmenyuk, T.; Bellinghausen, I.; Heydenreich, B.; Ilchmann, A.; Toda, M.; Grabbe, S.; Saloga, J. Effects of glycation of the model food allergen ovalbumin on antigen uptake and presentation by human dendritic cells. Immunology 2010, 129, 437–445. [Google Scholar] [CrossRef]
- Ilchmann, A.; Burgdorf, S.; Scheurer, S.; Waibler, Z.; Nagai, R.; Wellner, A.; Yamamoto, Y.; Yamamoto, H.; Henle, T.; Kurts, C.; et al. Glycation of a food allergen by the Maillard reaction enhances its T-cell immunogenicity: Role of macrophage scavenger receptor class A type I and II. J. Allergy Clin. Immunol. 2010, 125, 175–183.e111. [Google Scholar] [CrossRef]
- Teodorowicz, M.; Van Neerven, J.; Savelkoul, H. Food processing: The influence of the maillard reaction on immunogenicity and allergenicity of food proteins. Nutrients 2017, 9, 835. [Google Scholar] [CrossRef] [PubMed]
- Ott, C.; Jacobs, K.; Haucke, E.; Navarrete Santos, A.; Grune, T.; Simm, A. Role of advanced glycation end products in cellular signaling. Redox Biol. 2014, 2, 411–429. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ohgami, N.; Nagai, R.; Ikemoto, M.; Arai, H.; Kuniyasu, A.; Horiuchi, S.; Nakayama, H. CD36, a Member of the Class B Scavenger Receptor Family, as a Receptor for Advanced Glycation End Products. J. Biol. Chem. 2001, 276, 3195–3202. [Google Scholar] [CrossRef] [Green Version]
- Ohgami, N.; Nagai, R.; Miyazaki, A.; Ikemoto, M.; Arai, H.; Horiuchi, S.; Nakayama, H. Scavenger Receptor Class B Type I-mediated Reverse Cholesterol Transport Is Inhibited by Advanced Glycation End Products. J. Biol. Chem. 2001, 276, 13348–13355. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Araki, N.; Higashi, T.; Mori, T.; Shibayama, R.; Kawabe, Y.; Kodama, T.; Takahashi, K.; Shichiri, M.; Horiuchi, S. Macrophage Scavenger Receptor Mediates the Endocytic Uptake and Degradation of Advanced Glycation End Products of the Maillard Reaction. Eur. J. Biochem. 1995, 230, 408–415. [Google Scholar] [CrossRef] [PubMed]
- Vlassara, H.; Li, Y.M.; Imani, F.; Wojciechowicz, D.; Yang, Z.; Liu, F.T.; Cerami, A. Identification of galectin-3 as a high-affinity binding protein for advanced glycation end products (AGE): A new member of the AGE-receptor complex. Mol. Med. 1995, 1, 634–646. [Google Scholar] [CrossRef] [Green Version]
- Kierdorf, K.; Fritz, G. RAGE regulation and signaling in inflammation and beyond. J. Leukoc. Biol. 2013, 94, 55–68. [Google Scholar] [CrossRef]
- Gough, P.J.; Gordon, S. The role of scavenger receptors in the innate immune system. Microbes. Infect. 2000, 2, 305–311. [Google Scholar] [CrossRef]
- Díaz-Alvarez, L.; Ortega, E. The Many Roles of Galectin-3, a Multifaceted Molecule, in Innate Immune Responses against Pathogens. Mediat. Inflamm. 2017, 2017. [Google Scholar] [CrossRef] [Green Version]
- Milkovska-Stamenova, S.; Mnatsakanyan, R.; Hoffmann, R. Protein carbonylation sites in bovine raw milk and processed milk products. Food Chem. 2017, 229, 417–424. [Google Scholar] [CrossRef]
- Pischetsrieder, M.; Henle, T. Glycation products in infant formulas: Chemical, analytical and physiological aspects. Amino Acids 2012, 42, 1111–1118. [Google Scholar] [CrossRef] [PubMed]
- Heilmann, M.; Wellner, A.; Gadermaier, G.; Ilchmann, A.; Briza, P.; Krause, M.; Nagai, R.; Burgdorf, S.; Scheurer, S.; Vieths, S.; et al. Ovalbumin modified with pyrraline, a maillard reaction product, shows enhanced T-cell immunogenicity. J. Biol. Chem. 2014, 289, 7919–7928. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kislinger, T.; Fu, C.; Huber, B.; Qu, W.; Taguchi, A.; Yan, S.D.; Hofmann, M.; Yan, S.F.; Pischetsrieder, M.; Stern, D.; et al. N(ε)-(carboxymethyl)lysine adducts of proteins are ligands for receptor for advanced glycation end products that activate cell signaling pathways and modulate gene expression. J. Biol. Chem. 1999, 274, 31740–31749. [Google Scholar] [CrossRef] [Green Version]
- Glorieux, G.; Helling, R.; Henle, T.; Brunet, P.; Deppisch, R.; Lameire, N.; Vanholder, R. In vitro evidence for immune activating effect of specific AGE structures retained in uremia. Kidney Int. 2004, 66, 1873–1880. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Buetler, T.M.; Leclerc, E.; Baumeyer, A.; Latado, H.; Newell, J.; Adolfsson, O.; Parisod, V.; Richoz, J.; Maurer, S.; Foata, F.; et al. Nε-carboxymethyllysine-modified proteins are unable to bind to RAGE and activate an inflammatory response. Mol. Nutr. Food Res. 2008, 52, 370–378. [Google Scholar] [CrossRef] [PubMed]
- Deng, Y.; Govers, C.; Bastiaan-Net, S.; van der Hulst, N.; Hettinga, K.; Wichers, H.J. Hydrophobicity and aggregation, but not glycation, are key determinants for uptake of thermally processed β-lactoglobulin by THP-1 macrophages. Food Res. Int. 2019, 120, 102–113. [Google Scholar] [CrossRef]
- Liu, F.; Teodorowicz, M.; Wichers, H.J.; Van Boekel, M.A.J.S.; Hettinga, K.A. Generation of Soluble Advanced Glycation End Products Receptor (sRAGE)-Binding Ligands during Extensive Heat Treatment of Whey Protein/Lactose Mixtures Is Dependent on Glycation and Aggregation. J. Agric. Food Chem. 2016, 64, 6477–6486. [Google Scholar] [CrossRef]
- Zenker, H.E.; Ewaz, A.; Deng, Y.; Savelkoul, H.F.J.; Van Neerven, R.J.J.; De Jong, N.; Wichers, H.J.; Hettinga, K.A.; Teodorowicz, M. Differential effects of dry vs. Wet heating of β-lactoglobulin on formation of sRAGE binding ligands and sIgE epitope recognition. Nutrients 2019, 11, 1432. [Google Scholar] [CrossRef] [Green Version]
- Bongarzone, S.; Savickas, V.; Luzi, F.; Gee, A.D. Targeting the Receptor for Advanced Glycation Endproducts (RAGE): A Medicinal Chemistry Perspective. J. Med. Chem. 2017, 60, 7213–7232. [Google Scholar] [CrossRef] [Green Version]
- Ng-Kwai-Hang, K.F.; Kim, S. Different amounts of β-lactoglobulin A and B in milk from heterozygous AB cows. Int. Dairy J. 1996, 6, 689–695. [Google Scholar] [CrossRef]
- Kawabata, K.; Yoshikawa, H.; Saruwatari, K.; Akazawa, Y.; Inoue, T.; Kuze, T.; Sayo, T.; Uchida, N.; Sugiyama, Y. The presence of Nε-(Carboxymethyl) lysine in the human epidermis. Biochim. et Biophys. Acta (BBA) Proteins Proteom. 2011, 1814, 1246–1252. [Google Scholar] [CrossRef] [PubMed]
- Bartakova, V.; Kollarova, R.; Kuricova, K.; Sebekova, K.; Belobradkova, J.; Kankova, K. Serum carboxymethyl-lysine, a dominant advanced glycation end product, is increased in women with gestational diabetes mellitus. Biomed. Pap. 2016, 160, 70–75. [Google Scholar] [CrossRef] [PubMed]
- Gaens, K.H.J.; Ferreira, I.; Van De Waarenburg, M.P.H.; Van Greevenbroek, M.M.; Van Der Kallen, C.J.H.; Dekker, J.M.; Nijpels, G.; Rensen, S.S.; Stehouwer, C.D.A.; Schalkwijk, C.G. Protein-Bound Plasma Nε-(Carboxymethyl)lysine Is Inversely Associated with Central Obesity and Inflammation and Significantly Explain a Part of the Central Obesity-Related Increase in Inflammation: The Hoorn and CODAM Studies. Arterioscler. Thromb. Vasc. Biol. 2015, 35, 2707–2713. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Gaens, K.H.J.; Niessen, P.M.G.; Rensen, S.S.; Buurman, W.A.; Greve, J.W.M.; Driessen, A.; Wolfs, M.G.M.; Hofker, M.H.; Bloemen, J.G.; Dejong, C.H.; et al. Endogenous formation of Nε-(carboxymethyl)lysine is increased in fatty livers and induces inflammatory markers in an in vitro model of hepatic steatosis. J. Hepatol. 2012, 56, 647–655. [Google Scholar] [CrossRef] [PubMed]
- Prosser, C.G.; Carpenter, E.A.; Hodgkinson, A.J. N ε -carboxymethyllysine in nutritional milk formulas for infants. Food Chem. 2019, 274, 886–890. [Google Scholar] [CrossRef]
- Cardoso, H.B.; Wierenga, P.A.; Gruppen, H.; Schols, H.A. Maillard induced aggregation of individual milk proteins and interactions involved. Food Chem. 2019, 276, 652–661. [Google Scholar] [CrossRef] [PubMed]
- Enomoto, H.; Li, C.P.; Morizane, K.; Ibrahim, H.R.; Sugimoto, Y.; Ohki, S.; Ohtomo, H.; Aoki, T. Glycation and phosphorylation of β-lactoglobulin by dry-heating: Effect on protein structure and some properties. J. Agric. Food Chem. 2007, 55, 2392–2398. [Google Scholar] [CrossRef]
- Biancalana, M.; Koide, S. Molecular mechanism of Thioflavin-T binding to amyloid fibrils. Biochim. et Biophys. Acta (BBA) Proteins Proteom. 2010, 1804, 1405–1412. [Google Scholar] [CrossRef] [Green Version]
- Gade Malmos, K.; Blancas-Mejia, L.M.; Weber, B.; Buchner, J.; Ramirez-Alvarado, M.; Naiki, H.; Otzen, D. ThT 101: A primer on the use of thioflavin T to investigate amyloid formation. Amyloid 2017, 24, 1–16. [Google Scholar] [CrossRef]
- Morgan, F.; Léonil, J.; Mollé, D.; Bouhallab, S. Modification of bovine β-lactoglobulin by glycation in a powdered state or in an aqueous solution: Effect on association behavior and protein conformation. J. Agric. Food Chem. 1999, 47, 83–91. [Google Scholar] [CrossRef] [Green Version]
- Teodorowicz, M.; Hendriks, W.H.; Wichers, H.J.; Savelkoul, H.F.J. Immunomodulation by processed animal feed: The role of maillard reaction products and advanced glycation end-products (AGEs). Front. Immunol. 2018, 9. [Google Scholar] [CrossRef] [Green Version]
- Thornalley, P.J.; Battah, S.; Ahmed, N.; Karachalias, N.; Agalou, S.; Babaei-Jadidi, R.; Dawnay, A. Quantitative screening of advanced glycation endproducts in cellular and extracellular proteins by tandem mass spectrometry. Biochem. J. 2003, 375, 581–592. [Google Scholar] [CrossRef] [PubMed]
- Fritz, G. RAGE: A single receptor fits multiple ligands. Trends Biochem. Sci. 2011, 36, 625–632. [Google Scholar] [CrossRef] [PubMed]
- Collot-Teixeira, S.; Martin, J.; McDermott-Roe, C.; Poston, R.; McGregor, J.L. CD36 and macrophages in atherosclerosis. Cardiovasc. Res. 2007, 75, 468–477. [Google Scholar] [CrossRef] [PubMed]
- Xue, J.; Rai, V.; Singer, D.; Chabierski, S.; Xie, J.; Reverdatto, S.; Burz, D.S.; Schmidt, A.M.; Hoffmann, R.; Shekhtman, A. Advanced glycation end product recognition by the receptor for AGEs. Structure 2011, 19, 722–732. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Jimenez-Dalmaroni, M.J.; Xiao, N.; Corper, A.L.; Verdino, P.; Ainge, G.D.; Larsen, D.S.; Painter, G.F.; Rudd, P.M.; Dwek, R.A.; Hoebe, K.; et al. Soluble CD36 ectodomain binds negatively charged diacylglycerol ligands and acts as a co-receptor for TLR2. PLoS ONE 2009, 4. [Google Scholar] [CrossRef] [PubMed]
- Modenutti, C.P.; Capurro, J.I.B.; Di Lella, S.; Martí, M.A. The Structural Biology of Galectin-Ligand Recognition: Current Advances in Modeling Tools, Protein Engineering, and Inhibitor Design. Front. Chem. 2019, 7. [Google Scholar] [CrossRef] [PubMed]
- Delgado-Andrade, C.; Fogliano, V. Dietary Advanced Glycosylation End-Products (dAGEs) and Melanoidins Formed through the Maillard Reaction: Physiological Consequences of their Intake. Annu. Rev. Food Sci. Technol. 2018, 9, 271–291. [Google Scholar] [CrossRef]
- Hellwig, M.; Matthes, R.; Peto, A.; Löbner, J.; Henle, T. N-ε-fructosyllysine and N-ε-carboxymethyllysine, but not lysinoalanine, are available for absorption after simulated gastrointestinal digestion. Amino Acids 2014, 46, 289–299. [Google Scholar] [CrossRef]
- Allen, F.; Tong, A.A.; Huang, A.Y. Unique transcompartmental bridge: Antigen-presenting cells sampling across endothelial and mucosal barriers. Front. Immunol. 2016, 7. [Google Scholar] [CrossRef] [Green Version]
- Akillioğlu, H.G.; Gökmen, V. Effects of hydrophobic and ionic interactions on glycation of casein during Maillard reaction. J. Agric. Food Chem. 2014, 62, 11289–11295. [Google Scholar] [CrossRef] [PubMed]
- Delatour, T.; Hegele, J.; Parisod, V.; Richoz, J.; Maurer, S.; Steven, M.; Buetler, T. Analysis of advanced glycation endproducts in dairy products by isotope dilution liquid chromatography-electrospray tandem mass spectrometry. The particular case of carboxymethyllysine. J. Chromatogr. A 2009, 1216, 2371–2381. [Google Scholar] [CrossRef] [PubMed]
- Mulet-Cabero, A.I.; Rigby, N.M.; Brodkorb, A.; Mackie, A.R. Dairy food structures influence the rates of nutrient digestion through different in vitro gastric behaviour. Food Hydrocoll. 2017, 67, 63–73. [Google Scholar] [CrossRef] [Green Version]
- Alizadeh-Pasdar, N.; Li-Chan, E.C.Y. Application of PRODAN fluorescent probe to measure surface hydrophobicity of proteins interacting with κ-carrageenan. Food Hydrocoll. 2001, 15, 285–294. [Google Scholar] [CrossRef]
Sample | CML Content [mg/g Protein] | CML Modified Lysine [%] |
---|---|---|
BLG-NT | 0.4 ± 0.3 a | 0.39 ± 0.3 a |
BLG-CML-1 | 28.0 ± 0.1 b | 17 ± 0.0 b |
BLG-CML-3 | 56.1 ± 0.1 cd | 34 ± 0.1 de |
BLG-CML-5 | 62.6 ± 1.3 d | 38 ± 0.8 d |
BLG-Lac-12 | 2.0 ± 0.2 a | 1.2 ± 0.1 a |
BLG-Lac-24 | 3.7 ± 0.4 a | 2.2 ± 0.2a |
BLG-Lac-48 | 4.4 ± 0.3 a | 2.7 ± 0.2 a |
BLG-H-12 | 1.6 ± 1.9 a | 1.0 ± 1.2 a |
BLG-H-24 | 0.3 ± 0.0 a | 0.2 ± 0.0 a |
BLG-H-48 | 0.4 ± 0.2 a | 0.2 ± 0.1 a |
BLG-Lac-12-CML | 46.4 ± 2.9 c | 28 ± 1.8 c |
BLG-Lac-24-CML | 50.3 ± 7.8 c | 31 ± 4.7 cd |
BLG-Lac-48-CML | 34.5 ± 1.9 b | 16 ± 0.9 b |
© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Share and Cite
Zenker, H.E.; Teodorowicz, M.; Ewaz, A.; van Neerven, R.J.J.; Savelkoul, H.F.J.; De Jong, N.W.; Wichers, H.J.; Hettinga, K.A. Binding of CML-Modified as Well as Heat-Glycated β-lactoglobulin to Receptors for AGEs Is Determined by Charge and Hydrophobicity. Int. J. Mol. Sci. 2020, 21, 4567. https://doi.org/10.3390/ijms21124567
Zenker HE, Teodorowicz M, Ewaz A, van Neerven RJJ, Savelkoul HFJ, De Jong NW, Wichers HJ, Hettinga KA. Binding of CML-Modified as Well as Heat-Glycated β-lactoglobulin to Receptors for AGEs Is Determined by Charge and Hydrophobicity. International Journal of Molecular Sciences. 2020; 21(12):4567. https://doi.org/10.3390/ijms21124567
Chicago/Turabian StyleZenker, Hannah E., Malgorzata Teodorowicz, Arifa Ewaz, R.J. Joost van Neerven, Huub F.J. Savelkoul, Nicolette W. De Jong, Harry J. Wichers, and Kasper A. Hettinga. 2020. "Binding of CML-Modified as Well as Heat-Glycated β-lactoglobulin to Receptors for AGEs Is Determined by Charge and Hydrophobicity" International Journal of Molecular Sciences 21, no. 12: 4567. https://doi.org/10.3390/ijms21124567