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

IF 1.9 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY
Jia Wang, Jiayin Liu, Qinghai Dong, Yang An, Jun Su, Hongliu Xie, Bo Sun, Jihua Liu
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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.

硫酸肝素对乳腺淀粉样变性的影响及β-酪蛋白形成的前原纤维的毒性
硫酸乙酰肝素(HS)作为介质通常参与炎症和纤维化。此外,前原纤维是淀粉样原纤维的中间体,通常引起细胞死亡和组织损伤,如阿尔茨海默病的淀粉样-β,帕金森病的α-突触核蛋白和II型糖尿病的胰岛淀粉样多肽。然而,相关研究很少涉及乳腺。因此,采用苏木精-伊红染色和硫黄素S染色等结合技术研究HS对乳腺淀粉样变性的影响。为了进一步研究β-酪蛋白形成的前原纤维对HC11细胞和乳腺的毒性,采用五聚甲酰基噻吩乙酸荧光分析、MTT法、Annexin V/PI染色和苏木精-伊红染色等梳理技术。结果表明,HS作为内源性分子,可同时诱导乳腺炎症和淀粉样纤维的形成,炎症与乳腺纤维化之间存在密切关系。此外,β-酪蛋白形成的前原纤维具有毒性,因为它能诱导HC11细胞死亡和凋亡,并引起大鼠乳腺炎症。因此,早期检查和识别乳腺前原纤维是值得考虑的,以预防疾病的发展,未来探索HS模拟物对乳腺淀粉样变性的损害和减轻炎症反应是有趣的。
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来源期刊
The Protein Journal
The Protein Journal 生物-生化与分子生物学
CiteScore
5.20
自引率
0.00%
发文量
57
审稿时长
12 months
期刊介绍: The Protein Journal (formerly the Journal of Protein Chemistry) publishes original research work on all aspects of proteins and peptides. These include studies concerned with covalent or three-dimensional structure determination (X-ray, NMR, cryoEM, EPR/ESR, optical methods, etc.), computational aspects of protein structure and function, protein folding and misfolding, assembly, genetics, evolution, proteomics, molecular biology, protein engineering, protein nanotechnology, protein purification and analysis and peptide synthesis, as well as the elucidation and interpretation of the molecular bases of biological activities of proteins and peptides. We accept original research papers, reviews, mini-reviews, hypotheses, opinion papers, and letters to the editor.
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