Serum amyloid P component promotes formation of distinct aggregated lysozyme morphologies and reduces toxicity in Drosophila flies expressing F57I lysozyme


Autoři: Liza Bergkvist aff001;  Daniel R. Richards aff002;  Ana Bernardo-Gancedo aff002;  Janet R. Kumita aff002;  Peter R. Nilsson aff001;  Ann-Christin Brorsson aff001
Působiště autorů: Division of Molecular Biotechnology, Department of Physics, Chemistry and Biology, Linköping University, Linköping, Sweden aff001;  Centre for Misfolding Diseases, Department of Chemistry, University of Cambridge, Cambridge, England, United Kingdom aff002
Vyšlo v časopise: PLoS ONE 15(1)
Kategorie: Research Article
doi: 10.1371/journal.pone.0227227

Souhrn

Many conflicting reports about the involvement of serum amyloid P component (SAP) in amyloid diseases have been presented over the years; SAP is known to be a universal component of amyloid aggregates but it has been suggested that it can both induce and suppress amyloid formation. By using our Drosophila model of systemic lysozyme amyloidosis, SAP has previously been shown to reduce the toxicity induced by the expression of the disease-associated lysozyme variant, F57I, in the Drosophila central nervous system. This study further investigates the involvement of SAP in modulating lysozyme toxicity using histochemistry and spectral analyses on the double transgenic WT and F57I lysozyme flies to probe; i) formation of aggregates, ii) morphological differences of the aggregated lysozyme species formed in the presence or absence of SAP, iii) location of lysozyme and iv) co-localisation of lysozyme and SAP in the fly brain. We found that SAP can counteract the toxicity (measured by the reduction in the median survival time) induced by F57I lysozyme by converting toxic F57I species into less toxic amyloid-like structures, as reflected by the spectral changes that p-FTAA undergoes when bound to lysozyme deposits in F57I-F57I-SAP flies as compared to F57I-F57I flies. Indeed, when SAP was introduced to in vitro lysozyme fibril formation, the endpoint fibrils had enhanced ThT fluorescence intensity as compared to lysozyme fibrils alone. This suggests that a general mechanism for SAP's role in amyloid diseases may be to promote the formation of stable, amyloid-like fibrils, thus decreasing the impact of toxic species formed along the aggregation pathway.

Klíčová slova:

Amyloid proteins – Amyloidosis – Drosophila melanogaster – Emission spectra – Fluorescence – Fluorescence imaging – Lysozyme – Toxicity


Zdroje

1. Tennent GA, Lovat LB, Pepys MB. Serum amyloid P component prevents proteolysis of the amyloid fibrils of Alzheimer disease and systemic amyloidosis. Proc Natl Acad Sci. 1995;92: 4299–303. doi: 10.1073/pnas.92.10.4299 7753801

2. Coker AR, Purvis A, Baker D, Pepys MB, Wood SP. Molecular chaperone properties of serum amyloid P component. FEBS Lett. 2000;473: 199–202. doi: 10.1016/s0014-5793(00)01530-1 10812074

3. Andersson K, Pokrzywa M, Dacklin I, Lundgren E. Inhibition of TTR aggregation-induced cell death—a new role for serum amyloid P component. PLoS One. 2013;8: e55766. doi: 10.1371/journal.pone.0055766 23390551

4. Pepys MB, Dyck RF, Beer FCDE, Skinner M, Immunological ASC. Binding of serum amyloid P-component (SAP) by amyloid fibrils Binding ofprotein SAP by amyloidfibrils. 1979;34: 284–293.

5. Rydh A, Suhr O, Hietala S, Åhlström KR, Pepys MB, Hawkins PN. Serum amyloid P component scintigraphy in familial amyloid polyneuropathy: regression of visceral amyloid following liver transplantation. Eur J Nucl Med. 1998;25: 709–713. doi: 10.1007/s002590050273 9662592

6. Richards DB, Cookson LM, Berges AC, Barton S V, Lane T, Ritter JM, et al. Therapeutic Clearance of Amyloid by Antibodies to Serum Amyloid P Component. N Engl J Med. 2015;373: 1106–14. doi: 10.1056/NEJMoa1504942 26176329

7. Pepys MB, Hawkins PN, Booth DR, Vigushin DM, Tennent GA, Soutar AK, et al. Human lysozyme gene mutations cause hereditary systemic amyloidosis. Nature. 1993;362: 553–7. doi: 10.1038/362553a0 8464497

8. Hansen NE, Karle H, Andersen V, Olgaard K. Lysozyme turnover in man. J Clin Invest. 1972;51: 1146–55. doi: 10.1172/JCI106907 4502451

9. Nasr SH, Dasari S, Mills JR, Theis JD, Zimmermann MT, Fonseca R, et al. Hereditary Lysozyme Amyloidosis Variant p.Leu102Ser Associates with Unique Phenotype. J Am Soc Nephrol. 2017;28: 431–438. doi: 10.1681/ASN.2016090951 28049649

10. Sattianayagam PT, Gibbs SDJ, Rowczenio D, Pinney JH, Wechalekar a D, Gilbertson J a, et al. Hereditary lysozyme amyloidosis—phenotypic heterogeneity and the role of solid organ transplantation. J Intern Med. 2012;272: 36–44. doi: 10.1111/j.1365-2796.2011.02470.x 21988333

11. Canet D, Sunde M, Last AM, Miranker A, Spencer A, Robinson CV, et al. Mechanistic studies of the folding of human lysozyme and the origin of amyloidogenic behavior in its disease-related variants. Biochemistry. 1999;38: 6419–27. doi: 10.1021/bi983037t 10350460

12. Malisauskas M, Ostman J, Darinskas A, Zamotin V, Liutkevicius E, Lundgren E, et al. Does the cytotoxic effect of transient amyloid oligomers from common equine lysozyme in vitro imply innate amyloid toxicity? J Biol Chem. 2005;280: 6269–6275. doi: 10.1074/jbc.M407273200 15576361

13. Gharibyan AL, Zamotin V, Yanamandra K, Moskaleva OS, Margulis BA, Kostanyan IA, et al. Lysozyme Amyloid Oligomers and Fibrils Induce Cellular Death via Different Apoptotic/Necrotic Pathways. J Mol Biol. 2007;365: 1337–1349. doi: 10.1016/j.jmb.2006.10.101 17134716

14. Kumita JR, Helmfors L, Williams J, Luheshi LM, Menzer L, Dumoulin M, et al. Disease-related amyloidogenic variants of human lysozyme trigger the unfolded protein response and disturb eye development in Drosophila melanogaster. FASEB J. 2012;26: 192–202. doi: 10.1096/fj.11-185983 21965601

15. Helmfors L, Bergkvist L, Brorsson AC. Serum amyloid P component ameliorates neurological damage caused by expressing a lysozyme variant in the central nervous system of Drosophila melanogaster. PLoS One. 2016;11: 1–16. doi: 10.1371/journal.pone.0159294 27428539

16. Hammarström P, Simon R, Nyström S, Konradsson P, Åslund A, Nilsson KPR. A fluorescent pentameric thiophene derivative detects in vitro-formed prefibrillar protein aggregates. Biochemistry. 2010;49: 6838–6845. doi: 10.1021/bi100922r 20604540

17. Arja K, Sjölander D, Åslund A, Prokop S, Heppner FL, Konradsson P, et al. Enhanced fluorescent assignment of protein aggregates by an oligothiophene-porphyrin-based amyloid ligand. Macromol Rapid Commun. 2013;34: 723–730. doi: 10.1002/marc.201200817 23468206

18. Magnusson K, Simon R, Sjolander D, Sigurdson CJ, Hammarstrom P, Nilsson KPR. Multimodal fluorescence microscopy of prion strain specific PrP deposits stained by thiophene-based amyloid ligands. Prion. 2014;8: 319–329. doi: 10.4161/pri.29239 25495506

19. Sjolander D, Rocken C, Westermark P, Westermark GT, Nilsson KPR, Hammarstrom P. Establishing the fluorescent amyloid ligand h-FTAA for studying human tissues with systemic and localized amyloid. Amyloid. 2016;6129: 1–11. doi: 10.3109/13506129.2016.1158159 26987044

20. Jonson M, Nyström S, Sandberg A, Carlback M, Michno W, Hanrieder J, et al. Aggregated Aβ1–42 is selectively toxic for neurons, whereas glial cells produce mature fibrils with low toxicity in Drosophila. Cell Chem Biol. 2018;25: 595–610.e5. doi: 10.1016/j.chembiol.2018.03.006 29657084

21. Hagan CL, Johnson RJK, Dhulesia A, Dumoulin M, Dumont J, De Genst E, et al. A non-natural variant of human lysozyme (I59T) mimics the in vitro behaviour of the I56T variant that is responsible for a form of familial amyloidosis. Protein Eng Des Sel. 2010;23: 499–506. doi: 10.1093/protein/gzq023 20382744

22. Ahn M, Waudby CA, Bernardo-Gancedo A, De Genst E, Dhulesia A, Salvatella X, et al. Application of lysine-specific labeling to detect transient interactions present during human lysozyme amyloid fibril formation. Sci Rep. 2017;7: 15018. doi: 10.1038/s41598-017-14739-5 29101328

23. Brand a H, Perrimon N. Targeted gene expression as a means of altering cell fates and generating dominant phenotypes. Development. 1993;118: 401–15. 8223268

24. Jonson M, Pokrzywa M, Starkenberg A, Hammarstrom P, Thor S. Systematic Aβ analysis in Drosophila reveals high toxicity for the 1–42, 3–42 and 11–42 peptides, and emphasizes N- and C-terminal residues. PLoS One. 2015;10: e0133272. doi: 10.1371/journal.pone.0133272 26208119

25. Bergkvist L, Sandin L, Kågedal K, Brorsson A-C. AβPP processing results in greater toxicity per amount of Aβ 1–42 than individually expressed and secreted Aβ 1–42 in Drosophila melanogaster. Biol Open. 2016; 1030–1039. doi: 10.1242/bio.017194 27387531

26. Aslund A, Sigurdson CJ, Klingstedt T, Grathwohl S, Bolmont T, Dickstein DL, et al. Novel pentameric thiophene derivatives for in vitro and in vivo optical imaging of a plethora of protein aggregates in cerebral amyloidoses. ACS Chem Biol. 2009;4: 673–84. doi: 10.1021/cb900112v 19624097

27. Berg I, Nilsson KPR, Thor S, Hammarström P. Efficient imaging of amyloid deposits in Drosophila models of human amyloidoses. Nat Protoc. Nature Publishing Group; 2010;5: 935–44. doi: 10.1038/nprot.2010.41 20431539

28. Klingstedt T, Aslund A, Simon RA, Johansson LBG, Mason JJ, Nyström S, et al. Synthesis of a library of oligothiophenes and their utilization as fluorescent ligands for spectral assignment of protein aggregates. Org Biomol Chem. 2011;9: 8356–70. doi: 10.1039/c1ob05637a 22051883

29. Klingstedt T, Blechschmidt C, Nogalska A, Prokop S, Häggqvist B, Danielsson O, et al. Luminescent Conjugated Oligothiophenes for Sensitive Fluorescent Assignment of Protein Inclusion Bodies. ChemBioChem. 2013;14: 607–616. doi: 10.1002/cbic.201200731 23450708

30. Mossuto MF, Dhulesia A, Devlin G, Frare E, Kumita JR, de Laureto PP, et al. The Non-Core Regions of Human Lysozyme Amyloid Fibrils Influence Cytotoxicity. J Mol Biol. 2010;402: 783–796. doi: 10.1016/j.jmb.2010.07.005 20624399

31. Dumoulin M, Last AM, Desmyter A, Decanniere K, Canet D, Larsson G, et al. A camelid antibody fragment inhibits the formation of amyloid fibrils by human lysozyme. Nature. 2003;424: 783–8. doi: 10.1038/nature01870 12917687

32. Kumita JR, Poon S, Caddy GL, Hagan CL, Dumoulin M, Yerbury JJ, et al. The Extracellular Chaperone Clusterin Potently Inhibits Human Lysozyme Amyloid Formation by Interacting with Prefibrillar Species. J Mol Biol. 2007;369: 157–167. doi: 10.1016/j.jmb.2007.02.095 17407782

33. Yerbury JJ, Kumita JR, Meehan S, Dobson CM, Wilson MR. alpha2-Macroglobulin and haptoglobin suppress amyloid formation by interacting with prefibrillar protein species. J Biol Chem. 2009;284: 4246–54. doi: 10.1074/jbc.M807242200 19074141

34. Sigurdson CJ, Nilsson KPR, Hornemann S, Manco G, Polymenidou M, Schwarz P, et al. Prion strain discrimination using luminescent conjugated polymers. Nat Methods. 2007;4: 1023–1030. doi: 10.1038/nmeth1131 18026110

35. Ozawa D, Nomura R, Mangione PP, Hasegawa K, Okoshi T, Porcari R, et al. Multifaceted anti-amyloidogenic and pro-amyloidogenic effects of C-reactive protein and serum amyloid P component in vitro. Sci Rep. 2016;6: 29077. doi: 10.1038/srep29077 27380955

36. Malisauskas M, Darinskas A, Zamotin V V, Gharibyan A, Kostanyan IA, Morozova-Roche LA. Intermediate amyloid oligomers of lysozyme: Is their cytotoxicity a particular case or general rule for amyloid? Biochem. 2006;71: 505–12.

37. Janciauskiene S, García de Frutos P, Carlemalm E, Dahlbäck B, Eriksson S. Inhibition of Alzheimer beta-peptide fibril formation by serum amyloid P component. J Biol Chem. 1995;270: 26041–4. doi: 10.1074/jbc.270.44.26041 7592799

38. Hamazaki H. Amyloid P Component Promotes Aggregation of Alzheimer′s β-Amyloid Peptide. Biochem Biophys Res Commun. 1995;211: 349–353. doi: 10.1006/bbrc.1995.1819 7794242

39. Mold M, Shrive AK, Exley C. Serum amyloid P component accelerates the formation and enhances the stability of amyloid fibrils in a physiologically significant under-saturated solution of amyloid-β42. J Alzheimers Dis. 2012;29: 875–81. doi: 10.3233/JAD-2012-120076 22337829


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