Skip to main content

Advertisement

Log in

The Influence of Heparan Sulfate on Breast Amyloidosis and the Toxicity of the Pre-fibrils Formed by β-casein

  • Published:
The Protein Journal Aims and scope Submit manuscript

Abstract

Heparan sulfate (HS) as a mediator is usually involved in both inflammation and fibrosis. Besides, pre-fibrils are the intermediates of amyloid fibrils that usually cause cell death and tissue damage, like the amyloid-β in Alzheimer’s disease, α-synuclein in Parkinson disease and islet amyloid polypeptide in type II diabetes mellitus. However, the related study was involved rarely in breast. Therefore, the combing technologies including hematoxylin-eosin staining and thioflavin S staining were used to investigate the influence of HS on breast amyloidosis. To further study the toxicity of the pre-fibrils formed by β-casein on the HC11 cells and the breast mammary gland, the combing technologies including pentamer formyl thiophene acetic acid fluorescence analysis, MTT assay, Annexin V/PI staining and hematoxylin-eosin staining were performed. The results demonstrated that HS, acted as an endogenous molecule, induced the inflammation and amyloid fibril formation at the same time, and there was a close relationship between inflammation and fibrosis of breast. In addition, the pre-fibrils formed by β-casein were toxic because they induced the death and apoptosis of HC11 cells, as well as the inflammation of mammary gland of rats. Therefore, the early examination and identify of the pre-fibrils in the breast were worth considering to prevent the disease development, and it was interesting to explore the HS mimetics to impair the breast amyloidosis and attenuate the inflammatory response in the future.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

Data Availability

All data generated from this work are contained in the manuscript and its supplementary files.

Abbreviations

HS:

heparan sulfate

HE:

hematoxylin-eosin

ThS:

thioflavin S

p-FTAA:

pentamer formyl thiophene acetic acid

CA:

corpora amylacea

References

  1. Dobson CM, Ellis RJ, Fersht AR et al (2001) The structural basis of protein folding and its links with human disease. Philosophical Trans Royal Soc B-biological Sci 356:133–145

    Article  CAS  Google Scholar 

  2. Anfinsen CB (1973) Principles that Govern the Folding of Protein Chains. Science 181:223–230

    Article  CAS  Google Scholar 

  3. Zhou C, Lou K, Tatum K et al (2015) Differentiating Glomerular Inflammation from Fibrosis in a Bone Marrow Chimera for Rat Anti-Glomerular Basement Membrane Glomerulonephritis. Am J Nephrol 42:42–53

    Article  CAS  Google Scholar 

  4. Wang J, Tian JJ, Sun J et al (2020) Research Paper Two identified subsets of CD8 T cells in obstructed kidneys play different roles in inflammation and fibrosis. Aging-Us 12:17528–17540

    Article  Google Scholar 

  5. Homer RJ, Elias JA, Lee CG et al (2011) Modern Concepts on the Role of Inflammation in Pulmonary Fibrosis. Arch Pathol Lab Med 135:780–788

    Article  CAS  Google Scholar 

  6. Bengel FM, Ross TL (2019) Emerging imaging targets for infiltrative cardiomyopathy: Inflammation and fibrosis. J Nuclear Cardiol 26:208–216

    Article  Google Scholar 

  7. Bushman WA, Jerde TJ (2016) The role of prostate inflammation and fibrosis in lower urinary tract symptoms. Am J Physiology-Renal Physiol 311:F817–F821

    Article  CAS  Google Scholar 

  8. Ngendahayo P, Faverly D, Hérin M (2013) Primary breast amyloidosis presenting solely as nonpalpable microcalcifications: A case report with review of the literature. Int J Surg Pathol 21:177–180

    Article  Google Scholar 

  9. Jawahar A, Nagamine A, Gamez R (2018) Breast plasmacytoma with associated amyloidosis mimicking breast carcinoma. Breast J 24:1071–1073

    Article  Google Scholar 

  10. Shah S, Dodelzon K (2020) Breast amyloidosis presenting as bilateral breast masses. J Breast Imaging 2:172–173

    Article  Google Scholar 

  11. Pan K, Zhong QX (2015) Amyloid-like fibrils formed from intrinsically disordered caseins: physicochemical and nanomechanical properties. Soft Matter 11:5898–5904

    Article  CAS  Google Scholar 

  12. Wang J, Zhu H, Gan H et al (2020) The effect of heparan sulfate on promoting amyloid fibril formation by β-casein and their binding research with multi-spectroscopic approaches. J Photochem Photobiol B 202:111671–111671

    Article  CAS  Google Scholar 

  13. Schaefer L (2014) Complexity of Danger: The Diverse Nature of Damage-associated Molecular Patterns. J Biol Chem 289:35237–35245

    Article  CAS  Google Scholar 

  14. Zechendorf E, Vaßen P, Zhang J et al (2018) Heparan sulfate induces necroptosis in murine cardiomyocytes: A medical-in silico approach combining in vitro experiments and machine learning. Front Immunol 9:393–393

    Article  Google Scholar 

  15. Parish CR (2006) The role of heparan sulphate in inflammation. Nat Rev Immunol 6:633–643

    Article  CAS  Google Scholar 

  16. Parish CR (2005) Heparan sulfate and inflammation. Nat Immunol 6:861–862

    Article  CAS  Google Scholar 

  17. Lu J, Auduong L, White ES et al (2014) Up-regulation of heparan sulfate 6-O-sulfation in idiopathic pulmonary fibrosis. Am J Respir Cell Mol Biol 50:106–114

    Article  CAS  Google Scholar 

  18. Alhasan AA, Spielhofer J, Kusche-Gullberg M et al (2014) Role of 6-O-Sulfated Heparan Sulfate in Chronic Renal Fibrosis. J Biol Chem 289:20295–20306

    Article  CAS  Google Scholar 

  19. Verma M, Vats A, Taneja V (2015) Toxic species in amyloid disorders: Oligomers or mature fibrils. Annals of the Indian Academy of Neurology 18:138–145

    Article  Google Scholar 

  20. Ittner LM, Ke YD, Delerue F et al (2010) Dendritic Function of Tau Mediates Amyloid-β Toxicity in Alzheimer’s Disease Mouse Models. Cell 142:387–397

    Article  CAS  Google Scholar 

  21. Manczak M, Mao P, Calkins MJ et al (2010) Mitochondria-targeted antioxidants protect against amyloid-β toxicity in Alzheimer’s disease neurons. J Alzheimers Dis 20:S609–S631

    Article  Google Scholar 

  22. Schneider JS, Aras R, Williams CK et al (2019) GM1 Ganglioside Modifies α-Synuclein Toxicity and is Neuroprotective in a Rat α-Synuclein Model of Parkinson’s Disease. Sci Rep 9:8362

    Article  Google Scholar 

  23. Zhao J, Liang Q, Sun Q et al (2017) (-)-Epigallocatechin-3-gallate (EGCG) inhibits fibrillation, disaggregates amyloid fibrils of α-synuclein, and protects PC12 cells against α-synuclein-induced toxicity. RSC Adv 7:32508–32517

    Article  CAS  Google Scholar 

  24. Meng F, Abedini A, Plesner A et al (2010) The Flavanol (–)-Epigallocatechin 3-Gallate Inhibits Amyloid Formation by Islet Amyloid Polypeptide, Disaggregates Amyloid Fibrils, and Protects Cultured Cells against IAPP-Induced Toxicity. Biochemistry 49:8127–8133

    Article  CAS  Google Scholar 

  25. Rivera JF, Costes S, Gurlo T et al (2014) Autophagy defends pancreatic β cells from Human islet amyloid polypeptide-induced toxicity. J Clin Investig 124:3489–3500

    Article  CAS  Google Scholar 

  26. Nilsson KPR, Lindgren M, Hammarström P, Clifton (2018)N.J.)1779:485–496

    CAS  Google Scholar 

  27. Civitelli L, Sandin L, Nelson E et al (2016) The Luminescent Oligothiophene p-FTAA Converts Toxic Aβ1–42 Species into Nontoxic Amyloid Fibers with Altered Properties. J Biol Chem 291:9233–9243

    Article  CAS  Google Scholar 

  28. Göransson A-L, Nilsson KPR, Kågedal K et al (2012) Identification of distinct physiochemical properties of toxic prefibrillar species formed by Aβ peptide variants. Biochem Biophys Res Commun 420:895–900

    Article  Google Scholar 

  29. Espargaró A, Sabate R, Ventura S (2012) Thioflavin-S staining coupled to flow cytometry. A screening tool to detect in vivo protein aggregation. Mol Bioystems 8:2839–2844

    Article  Google Scholar 

  30. Claudon C, Francin M, Marchal E et al (1998) Proteic composition of corpora amylacea in the bovine mammary gland. Tissue Cell 30:589–595

    Article  CAS  Google Scholar 

  31. Reid IM (1972) Corpora amylacea of the bovine mammary gland. Histochemical and electron microscopic evidence for their amyloid nature. J Comp Pathol 82:409–IN409

    Article  CAS  Google Scholar 

  32. Beems RB, Gruys E, Spit BJ (1978) Amyloid in the Corpora Amylacea of the Rat Mammary Gland. Vet Pathol 15:347–352

    Article  CAS  Google Scholar 

  33. Taniyama H, Kitamura A, Kagawa Y et al (2000) Localized Amyloidosis in Canine Mammary Tumors. Vet Pathol 37:104–107

    Article  CAS  Google Scholar 

  34. Nickerson SC, Sordillo LM, Boddie NT et al (1985) Prevalence and ultrastructural characteristics of bovine mammary corpora amylacea during the lactation cycle. J Dairy Sci 68:709–717

    Article  CAS  Google Scholar 

  35. O’Callaghan P, Zhang X, Li J-P (2018) Heparan Sulfate Proteoglycans as Relays of Neuroinflammation. J Histochem Cytochemistry 66:305–319

    Article  Google Scholar 

  36. Lindahl B, Lindahl U (1997) Amyloid-specific Heparan Sulfate from Human Liver and Spleen. J Biol Chem 272:26091–26094

    Article  CAS  Google Scholar 

  37. Noborn F, Ancsin JB, Ubhayasekera W et al (2012) Heparan Sulfate Dissociates Serum Amyloid A (SAA) from Acute-phase High-density Lipoprotein, Promoting SAA Aggregation. J Biol Chem 287:25669–25677

    Article  CAS  Google Scholar 

  38. Stefani M (2012) Structural features and cytotoxicity of amyloid oligomers: Implications in Alzheimer’s disease and other diseases with amyloid deposits. Prog Neurobiol 99:226–245

    Article  CAS  Google Scholar 

  39. Stefani M (2010) Biochemical and biophysical features of both oligomer/fibril and cell membrane in amyloid cytotoxicity. FEBS J 277:4602–4613

    Article  CAS  Google Scholar 

  40. Siddiqi MK, Malik S, Majid N et al (2020) Cytotoxic species in amyloid-associated diseases: Oligomers or mature fibrils. In Protein Misfolding (Donev, R., ed.). pp. 333–369

  41. Shafiei SS, Guerrero-Munoz MJ, Castillo-Carranza DL (2017) Tau Oligomers: Cytotoxicity, Propagation, and Mitochondrial Damage. Frontiers in Aging Neuroscience 9

Download references

Acknowledgements

We acknowledged the all participants and the organizations that funded my research.

Funding

This work was supported by the Science and Technology Development Program of Jilin Province (Grant no. 20210402038GH and 20180101253JC), the Graduate Innovation Fund of Jilin University (Grant no. 101832020CX318), and the Project of Bethune Plan from Jilin University (Grant no.2018B01).

Author information

Authors and Affiliations

Authors

Contributions

Jia Wang: Methodology, Writing-review and editing, Writing-original draft. Jiayin Liu: Validation. Qinghai Dong: Data curation. Yang An: Software. Jun Su: Formal analysis. Hongliu Xie: Supervision. Bo Sun: Resources. Jihua Liu: Conceptualization, Project administration.

Corresponding author

Correspondence to Jihua Liu.

Ethics declarations

Conflict of Interest

The authors declare that there are no competing interests associated with the manuscript.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic Supplementary Material

Below is the link to the electronic supplementary material.

Supplementary Material 1

Rights and permissions

Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, J., Liu, J., Dong, Q. et al. The Influence of Heparan Sulfate on Breast Amyloidosis and the Toxicity of the Pre-fibrils Formed by β-casein. Protein J 41, 543–549 (2022). https://doi.org/10.1007/s10930-022-10071-8

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10930-022-10071-8

Keywords

Navigation