The Influence of Ca2+ and Zn2+ on the Amyloid Fibril Formation by β-Casein

Jia	      Wang; Jihua	      Liu; Guangguang	      Du; Yang	      An; Chunfang	      Zhao; Baohua	      Zeng

doi:10.2174/0929866527666200318143533

Abstract

Background: The amyloid fibril formation in different tissues or organs is related to amyloidosis. The Ca2+, Zn2+ and heparan sulfate (HS) are important elements and compositions in human body, which play a key role in regulating various physiological activities. Recently, there are increasing evidence suggest that they are closely linked to the amyloid fibril formation.

Objective: The effect of Ca2+ and Zn2+ on the amyloid fibril formation by β-casein was investigated in the absence and presence of HS, which was significantly to explore the relationship between the concentration changes of Ca2+ and Zn2+ and amyloid fibril formation.

Methods: In this work, the influence of Ca2+ and Zn2+ on the β-casein fibril formation in the absence and presence of HS was investigated by various methods of Thioflavin T fluorescence assay, transmission electron microscopy and intrinsic fluorescence measure.

Results: The results demonstrated that Ca2+ and Zn2+ promoted the β-casein fibril formation. The effect of Ca2+ was greater than that of Zn2+. Meanwhile, the both metal ions had stronger effects when β-casein was incubated with HS together. In addition, it was also observed that the microenvironment of β-casein was changed because the intrinsic fluorescence peaks were red-shifted on the influence of Ca2+ and Zn2+.

Conclusion: Ca2+ and Zn2+ were capable of promoting the β-casein fibril formation in the both absence and presence of HS. This work set up the foundation for further researching of the amyloidosis pathogenesis and provided new insight for us to understand relationship between the inflammation and amyloidosis.

Keywords: β-casein, Ca2+, Zn2+, HS, amyloid fibril formation, mammary gland.

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[1] 
Comenzo, R.L. Amyloidosis. Curr. Treat. Options Oncol.,  2006, 7(3), 225-236.
[http://dx.doi.org/10.1007/s11864-006-0015-8] [PMID:  16615878] 
[2] 
Röcken, C.; Kronsbein, H.; Sletten, K.; Roessner, A.; Bässler, R. Amyloidosis of the breast. Virchows Arch.,  2002, 440(5), 527-535.
[http://dx.doi.org/10.1007/s00428-001-0555-z] [PMID:  12021928] 
[3] 
Fu, K.; Bassett, L.W. Mammographic findings of diffuse amyloidosis and carcinoma of the breast. AJR Am. J. Roentgenol.,  2001, 177(4), 901-902.
[http://dx.doi.org/10.2214/ajr.177.4.1770901] [PMID:  11566701] 
[4] 
Ngendahayo, P.; Faverly, D.; Hérin, M. Primary breast amyloidosis presenting solely as nonpalpable microcalcifications: A case report with review of the literature. Int. J. Surg. Pathol.,  2013, 21(2), 177-180.
[http://dx.doi.org/10.1177/1066896912457203] [PMID:  22976248] 
[5] 
Gluck, B.S.; Cabrera, J.; Strauss, B.; Ricca, R.; Brancaccio, W.; Tamsen, A. Amyloid deposition of the breast. AJR Am. J. Roentgenol.,  2000, 175(6), 1590-1590.
[http://dx.doi.org/10.2214/ajr.175.6.1751590] [PMID:  11090381] 
[6] 
Athanasiou, A.; Vanel, D.; Tomasic, G.; Bidault, F.; Balleyguier, C. Quiz. Primary breast amyloidosis. Eur. J. Radiol.,  2007, 61(2), 184-186.
[http://dx.doi.org/10.1016/j.ejrad.2006.08.031] [PMID:  17166682] 
[7] 
Singh, H.; Ye, A. Interactions and functionality of milk proteins in food emulsions. In: Milk Proteins from Expression to Food; Thompson, A.; Boland, M.; Singh, H., Eds.; Academic Press: Cambridge, MA, 2008, pp. 321-345.
[http://dx.doi.org/10.1016/B978-0-12-374039-7.00011-8] 
[8] 
Holt, C.; Carver, J.A. Darwinian transformation of a ‘scarcely nutritious fluid’ into milk. J. Evol. Biol.,  2012, 25(7), 1253-1263.
[http://dx.doi.org/10.1111/j.1420-9101.2012.02509.x] [PMID:  22524460] 
[9] 
Atamer, Z.; Post, A.E.; Schubert, T.; Holder, A.; Boom, R.M.; Hinrichs, J. Bovine β-casein. Int. Dairy J.,  2017, 66, 115-125.
[http://dx.doi.org/10.1016/j.idairyj.2016.11.010] 
[10] 
Koudelka, T.; Hoffmann, P.; Carver, J.A. Dephosphorylation of α(s)- and β-caseins and its effect on chaperone activity: A structural and functional investigation. J. Agric. Food Chem.,  2009, 57(13), 5956-5964.
[http://dx.doi.org/10.1021/jf9008372] [PMID:  19527030] 
[11] 
Treweek, T.M.; Thorn, D.C.; Price, W.E.; Carver, J.A. The chaperone action of bovine milk αS1- and αS2-caseins and their associated form αS-casein. Arch. Biochem. Biophys.,  2011, 510(1), 42-52.
[http://dx.doi.org/10.1016/j.abb.2011.03.012] [PMID:  21457703] 
[12] 
Zatta, P.; Drago, D.; Bolognin, S.; Sensi, S.L. Alzheimer’s disease, metal ions and metal homeostatic therapy. Trends Pharmacol. Sci.,  2009, 30(7), 346-355.
[http://dx.doi.org/10.1016/j.tips.2009.05.002] [PMID:  19540003] 
[13] 
LeVine, H. III Thioflavine T interaction with synthetic Alzheimer’s disease β-amyloid peptides: Detection of amyloid aggregation in solution. Protein Sci.,  1993, 2(3), 404-410.
[http://dx.doi.org/10.1002/pro.5560020312] [PMID:  8453378] 
[14] 
Sivalingam, V.; Patel, B.K. Familial mutations in fibrinogen Aα (FGA) chain identified in renal amyloidosis increase in vitro amyloidogenicity of FGA fragment. Biochimie,  2016, 127, 44-49.
[http://dx.doi.org/10.1016/j.biochi.2016.04.020] [PMID:  27126074] 
[15] 
King, C.Y.; Tittmann, P.; Gross, H.; Gebert, R.; Aebi, M.; Wüthrich, K. Prion-inducing domain 2-114 of yeast Sup35 protein transforms in vitro into amyloid-like filaments. Proc. Natl. Acad. Sci. USA,  1997, 94(13), 6618-6622.
[http://dx.doi.org/10.1073/pnas.94.13.6618] [PMID:  9192614] 
[16] 
Sharma, N.; Sivalingam, V.; Maurya, S.; Prasad, A.; Khandelwal, P.; Yadav, S.C.; Patel, B.K. New insights into in vitro amyloidogenic properties of human serum albumin suggest considerations for therapeutic precautions. FEBS Lett.,  2015, 589(24 Pt B), 4033-4038.
[http://dx.doi.org/10.1016/j.febslet.2015.11.004] [PMID:  26554815] 
[17] 
Thorn, D.C.; Meehan, S.; Sunde, M.; Rekas, A.; Gras, S.L.; MacPhee, C.E.; Dobson, C.M.; Wilson, M.R.; Carver, J.A. Amyloid fibril formation by bovine milk κ-casein and its inhibition by the molecular chaperones alphaS- and β-casein. Biochemistry,  2005, 44(51), 17027-17036.
[http://dx.doi.org/10.1021/bi051352r] [PMID:  16363816] 
[18] 
Thorn, D.C.; Ecroyd, H.; Sunde, M.; Poon, S.; Carver, J.A. Amyloid fibril formation by bovine milk α s2-casein occurs under physiological conditions yet is prevented by its natural counterpart, α s1-casein. Biochemistry,  2008, 47(12), 3926-3936.
[http://dx.doi.org/10.1021/bi701278c] [PMID:  18302322] 
[19] 
Farrell, H.M., Jr; Cooke, P.H.; Wickham, E.D.; Piotrowski, E.G.; Hoagland, P.D. Environmental influences on bovine κ-casein: Reduction and conversion to fibrillar (amyloid) structures. J. Protein Chem.,  2003, 22(3), 259-273.
[http://dx.doi.org/10.1023/A:1025020503769] [PMID:  12962326] 
[20] 
Morgan, P.E.; Treweek, T.M.; Lindner, R.A.; Price, W.E.; Carver, J.A. Casein proteins as molecular chaperones. J. Agric. Food Chem.,  2005, 53(7), 2670-2683.
[http://dx.doi.org/10.1021/jf048329h] [PMID:  15796610] 
[21] 
Tei, M.; Uchida, K.; Chambers, J.K.; Harada, H.; Takahashi, M.; Nishimura, R.; Watanabe, M.; Nakayama, H. Mammary lipid-rich carcinoma with extensive amyloid deposition in a dog. J. Vet. Med. Sci.,  2012, 74(6), 809-811.
[http://dx.doi.org/10.1292/jvms.11-0482] [PMID:  22261147] 
[22] 
Miura, T.; Suzuki, K.; Kohata, N.; Takeuchi, H. Metal binding modes of Alzheimer’s amyloid β-peptide in insoluble aggregates and soluble complexes. Biochemistry,  2000, 39(23), 7024-7031.
[http://dx.doi.org/10.1021/bi0002479] [PMID:  10841784] 
[23] 
Yang, D.S.; McLaurin, J.; Qin, K.; Westaway, D.; Fraser, P.E. Examining the zinc binding site of the amyloid-β peptide. Eur. J. Biochem.,  2000, 267(22), 6692-6698.
[http://dx.doi.org/10.1046/j.1432-1327.2000.01767.x] [PMID:  11054124] 
[24] 
Parthasarathy, S.; Long, F.; Miller, Y.; Xiao, Y.; McElheny, D.; Thurber, K.; Ma, B.; Nussinov, R.; Ishii, Y. Molecular-level examination of Cu2+ binding structure for amyloid fibrils of 40-residue Alzheimer’s β by solid-state NMR spectroscopy. J. Am. Chem. Soc.,  2011, 133(10), 3390-3400.
[http://dx.doi.org/10.1021/ja1072178] [PMID:  21341665] 
[25] 
Binolfi, A.; Valiente-Gabioud, A.A.; Duran, R.; Zweckstetter, M.; Griesinger, C.; Fernandez, C.O. Exploring the structural details of Cu(I) binding to α-synuclein by NMR spectroscopy. J. Am. Chem. Soc.,  2011, 133(2), 194-196.
[http://dx.doi.org/10.1021/ja107842f] [PMID:  21158432] 
[26] 
Binolfi, A.; Rasia, R.M.; Bertoncini, C.W.; Ceolin, M.; Zweckstetter, M.; Griesinger, C.; Jovin, T.M.; Fernández, C.O. Interaction of α-synuclein with divalent metal ions reveals key differences: A link between structure, binding specificity and fibrillation enhancement. J. Am. Chem. Soc.,  2006, 128(30), 9893-9901.
[http://dx.doi.org/10.1021/ja0618649] [PMID:  16866548] 
[27] 
Pappalardo, G.; Milardi, D.; Magrì, A.; Attanasio, F.; Impellizzeri, G.; La Rosa, C.; Grasso, D.; Rizzarelli, E. Environmental factors differently affect human and rat IAPP: Conformational preferences and membrane interactions of IAPP17-29 peptide derivatives. Chemistry,  2007, 13(36), 10204-10215.
[http://dx.doi.org/10.1002/chem.200700576] [PMID:  17902185] 
[28] 
Milardi, D.; Sciacca, M.F.M.; Pappalardo, M.; Grasso, D.M.; La Rosa, C. The role of aromatic side-chains in amyloid growth and membrane interaction of the islet amyloid polypeptide fragment LANFLVH. Eur. Biophys. J.,  2011, 40(1), 1-12.
[http://dx.doi.org/10.1007/s00249-010-0623-x] [PMID:  20809197] 
[29] 
Brender, J.R.; Hartman, K.; Nanga, R.P.R.; Popovych, N.; de la Salud Bea, R.; Vivekanandan, S.; Marsh, E.N.G.; Ramamoorthy, A. Role of zinc in human islet amyloid polypeptide aggregation. J. Am. Chem. Soc.,  2010, 132(26), 8973-8983.
[http://dx.doi.org/10.1021/ja1007867] [PMID:  20536124] 
[30] 
Salamekh, S.; Brender, J.R.; Hyung, S.J.; Nanga, R.P.R.; Vivekanandan, S.; Ruotolo, B.T.; Ramamoorthy, A. A two-site mechanism for the inhibition of IAPP amyloidogenesis by zinc. J. Mol. Biol.,  2011, 410(2), 294-306.
[http://dx.doi.org/10.1016/j.jmb.2011.05.015] [PMID:  21616080] 
[31] 
Morgan, C.J.; Gelfand, M.; Atreya, C.; Miranker, A.D. Kidney dialysis-associated amyloidosis: A molecular role for copper in fiber formation. J. Mol. Biol.,  2001, 309(2), 339-345.
[http://dx.doi.org/10.1006/jmbi.2001.4661] [PMID:  11371157] 
[32] 
Verdone, G.; Corazza, A.; Viglino, P.; Pettirossi, F.; Giorgetti, S.; Mangione, P.; Andreola, A.; Stoppini, M.; Bellotti, V.; Esposito, G. The solution structure of human β2-microglobulin reveals the prodromes of its amyloid transition. Protein Sci.,  2002, 11(3), 487-499.
[http://dx.doi.org/10.1110/ps.29002] [PMID:  11847272] 
[33] 
Villanueva, J.; Hoshino, M.; Katou, H.; Kardos, J.; Hasegawa, K.; Naiki, H.; Goto, Y. Increase in the conformational flexibility of β 2-microglobulin upon copper binding: A possible role for copper in dialysis-related amyloidosis. Protein Sci.,  2004, 13(3), 797-809.
[http://dx.doi.org/10.1110/ps.03445704] [PMID:  14767076] 
[34] 
Eakin, C.M.; Knight, J.D.; Morgan, C.J.; Gelfand, M.A.; Miranker, A.D. Formation of a copper specific binding site in non-native states of β-2-microglobulin. Biochemistry,  2002, 41(34), 10646-10656.
[http://dx.doi.org/10.1021/bi025944a] [PMID:  12186550] 
[35] 
Massi, F.; Straub, J.E. Energy landscape theory for Alzheimer’s amyloid β-peptide fibril elongation. Proteins,  2001, 42(2), 217-229.
[http://dx.doi.org/10.1002/1097-0134(20010201)42:2<217:AID-PROT90>3.0.CO;2-N] [PMID:  11119646] 
[36] 
Miller, Y.; Ma, B.; Nussinov, R. Polymorphism of Alzheimer’s Abeta17-42 (p3) oligomers: The importance of the turn location and its conformation. Biophys. J.,  2009, 97(4), 1168-1177.
[http://dx.doi.org/10.1016/j.bpj.2009.05.042] [PMID:  19686665] 
[37] 
Miller, Y.; Ma, B.; Nussinov, R. Metal binding sites in amyloid oligomers: Complexes and mechanisms. Coord. Chem. Rev.,  2012, 256(19-20), 2245-2252.
[http://dx.doi.org/10.1016/j.ccr.2011.12.022] 
[38] 
Tõugu, V.; Karafin, A.; Zovo, K.; Chung, R.S.; Howells, C.; West, A.K.; Palumaa, P. Zn(II)- and Cu(II)-induced non-fibrillar aggregates of amyloid-beta (1-42) peptide are transformed to amyloid fibrils, both spontaneously and under the influence of metal chelators. J. Neurochem.,  2009, 110(6), 1784-1795.
[http://dx.doi.org/10.1111/j.1471-4159.2009.06269.x] [PMID:  19619132] 
[39] 
Yoshiike, Y.; Tanemura, K.; Murayama, O.; Akagi, T.; Murayama, M.; Sato, S.; Sun, X.; Tanaka, N.; Takashima, A. New insights on how metals disrupt amyloid β-aggregation and their effects on amyloid-β cytotoxicity. J. Biol. Chem.,  2001, 276(34), 32293-32299.
[http://dx.doi.org/10.1074/jbc.M010706200] [PMID:  11423547] 
[40] 
Raman, B.; Ban, T.; Yamaguchi, K.; Sakai, M.; Kawai, T.; Naiki, H.; Goto, Y. Metal ion-dependent effects of clioquinol on the fibril growth of an amyloid beta peptide. J. Biol. Chem.,  2005, 280(16), 16157-16162.
[http://dx.doi.org/10.1074/jbc.M500309200] [PMID:  15718230] 
[41] 
House, E.; Collingwood, J.; Khan, A.; Korchazkina, O.; Berthon, G.; Exley, C. Aluminium, iron, zinc and copper influence the in vitro formation of amyloid fibrils of Abeta42 in a manner which may have consequences for metal chelation therapy in Alzheimer’s disease. J. Alzheimers Dis.,  2004, 6(3), 291-301.
[http://dx.doi.org/10.3233/JAD-2004-6310] [PMID:  15201484] 
[42] 
Innocenti, M.; Salvietti, E.; Guidotti, M.; Casini, A.; Bellandi, S.; Foresti, M.L.; Gabbiani, C.; Pozzi, A.; Zatta, P.; Messori, L. Trace copper(II) or zinc(II) ions drastically modify the aggregation behavior of amyloid-beta1-42: An AFM study. J. Alzheimers Dis.,  2010, 19(4), 1323-1329.
[http://dx.doi.org/10.3233/JAD-2010-1338] [PMID:  20061619] 
[43] 
Ryu, J.; Girigoswami, K.; Ha, C.; Ku, S.H.; Park, C.B. Influence of multiple metal ions on beta-amyloid aggregation and dissociation on a solid surface. Biochemistry,  2008, 47(19), 5328-5335.
[http://dx.doi.org/10.1021/bi800012e] [PMID:  18422346] 
[44] 
Durand, J.; Meloni, G.; Talmard, C.; Vašák, M.; Faller, P. Zinc release of Zn7-metallothionein-3 induces fibrillar type amyloid-β aggregates. Metallomics,  2010, 2(11), 741-744.
[http://dx.doi.org/10.1039/c0mt00027b] [PMID:  21072365] 
[45] 
Huang, X.; Atwood, C.S.; Moir, R.D.; Hartshorn, M.A.; Tanzi, R.E.; Bush, A.I. Trace metal contamination initiates the apparent auto-aggregation, amyloidosis, and oligomerization of Alzheimer’s Abeta peptides. J. Biol. Inorg. Chem.,  2004, 9(8), 954-960.
[http://dx.doi.org/10.1007/s00775-004-0602-8] [PMID:  15578276] 
[46] 
Bolognin, S.; Zatta, P.; Drago, D.; Tognon, G.; Parnigotto, P.P.; Ricchelli, F. Mutual stimulation of beta-amyloid fibrillogenesis by clioquinol and divalent metals. Neuromolecular Med.,  2008, 10(4), 322-332.
[http://dx.doi.org/10.1007/s12017-008-8046-x] [PMID:  18712494] 
[47] 
Chen, T.; Wang, X.; He, Y.; Zhang, C.; Wu, Z.; Liao, K.; Wang, J.; Guo, Z. Effects of cyclen and cyclam on zinc(II)- and copper(II)-induced amyloid beta-peptide aggregation and neurotoxicity. Inorg. Chem.,  2009, 48(13), 5801-5809.
[http://dx.doi.org/10.1021/ic900025x] [PMID:  19496588] 
[48] 
Rodríguez-Rodríguez, C.; Sánchez de Groot, N.; Rimola, A.; Alvarez-Larena, A.; Lloveras, V.; Vidal-Gancedo, J.; Ventura, S.; Vendrell, J.; Sodupe, M.; González-Duarte, P. Design, selection, and characterization of thioflavin-based intercalation compounds with metal chelating properties for application in Alzheimer’s disease. J. Am. Chem. Soc.,  2009, 131(4), 1436-1451.
[http://dx.doi.org/10.1021/ja806062g] [PMID:  19133767] 
[49] 
Ahmad, A.; Muzaffar, M.; Ingram, V.M. Ca(2+), within the physiological concentrations, selectively accelerates Abeta42 fibril formation and not Abeta40 in vitro. Biochim. Biophys. Acta,  2009, 1794(10), 1537-1548.
[http://dx.doi.org/10.1016/j.bbapap.2009.06.022] [PMID:  19595795] 
[50] 
Bode, D.C.; Baker, M.D.; Viles, J.H. Ion channel formation by amyloid-β42 oligomers but not amyloid-β40 in cellular membranes. J. Biol. Chem.,  2017, 292(4), 1404-1413.
[http://dx.doi.org/10.1074/jbc.M116.762526] [PMID:  27927987] 
[51] 
Hovey, R.C.; Trott, J.F.; Vonderhaar, B.K. Establishing a framework for the functional mammary gland: From endocrinology to morphology. J. Mammary Gland Biol. Neoplasia,  2002, 7(1), 17-38.
[http://dx.doi.org/10.1023/A:1015766322258] [PMID:  12160083] 
[52] 
Liu, B.Y.; McDermott, S.P.; Khwaja, S.S.; Alexander, C.M.; Dove, W.F. The transforming activity of Wnt effectors correlates with their ability to induce the accumulation of mammary progenitor cells. Proc. Natl. Acad. Sci. USA,  2004, 101(12), 4158-4163.
[http://dx.doi.org/10.1073/pnas.0400699101] [PMID:  15020770] 
[53] 
Shukla, D.; Spear, P.G. Herpesviruses and heparan sulfate: An intimate relationship in aid of viral entry. J. Clin. Invest.,  2001, 108(4), 503-510.
[http://dx.doi.org/10.1172/JCI200113799] [PMID:  11518721] 
[54] 
Bishop, J.R.; Schuksz, M.; Esko, J.D. Heparan sulphate proteoglycans fine-tune mammalian physiology. Nature,  2007, 446(7139), 1030-1037.
[http://dx.doi.org/10.1038/nature05817] [PMID:  17460664] 
[55] 
Ancsin, J.B. Amyloidogenesis: Historical and modern observations point to heparan sulfate proteoglycans as a major culprit. Amyloid,  2003, 10(2), 67-79.
[http://dx.doi.org/10.3109/13506120309041728] [PMID:  12964414] 
[56] 
Vessely, C.R.; Carpenter, J.F.; Schwartz, D.K. Calcium-induced changes to the molecular conformation and aggregate structure of β-casein at the air-water interface. Biomacromolecules,  2005, 6(6), 3334-3344.
[http://dx.doi.org/10.1021/bm050353w] [PMID:  16283763] 

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DOI https://dx.doi.org/10.2174/0929866527666200318143533	Print ISSN 0929-8665
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The Influence of Ca²⁺ and Zn²⁺ on the Amyloid Fibril Formation by β-Casein

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Protein & Peptide Letters

The Influence of Ca2+ and Zn2+ on the Amyloid Fibril Formation by β-Casein

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The Influence of Ca²⁺ and Zn²⁺ on the Amyloid Fibril Formation by β-Casein