Saha Sarmistha, Mishra Abhijit
Materials Engineering, Indian Institute of Technology Gandhinagar, Palaj, Gandhinagar, India.
Department of Biotechnology, Institute of Applied Sciences & Humanities, GLA University, Mathura, Uttar Pradesh, 281406, India.
Urolithiasis. 2024 Dec 12;53(1):5. doi: 10.1007/s00240-024-01678-w.
The formation of polycrystalline aggregates in the glomerulus or other components of the urinary system is indisputably the most critical step in the formation of kidney stones and calcium oxalate monohydrate (CaCO·HO) is the most prevalent form. On the other hand, Annexin A1 (ANXA1), a calcium-binding protein, markedly increased on the apical surface of renal cells in CaCO-induced nephrolithiasis. In this regard, we identified the peptide motif responsible for calcium binding and redesigned it into a self-assembling peptide sequence without disturbing its binding selectivity for the CaCO interface. We developed a salt-dependent strategy to produce self-assembling spherical peptide nanoparticles by using aqueous solutions of R8 peptide and 16-amino acid designed peptide of net charge of -3 (WAEEFLKWLAFIEEFF). Peptide nanoparticles restored cell viability and reduced oxidative stress in MDCK cells triggered by CaCO crystals (80 µg cm) via Nrf2-HO-1 pathway activation. Peptide nanoparticles led to significant protection in urinary biochemistry and reducing calcifications without any toxicity.
肾小球或泌尿系统其他成分中多晶聚集体的形成无疑是肾结石形成过程中最关键的一步，而一水合草酸钙（CaCO·HO）是最常见的形式。另一方面，膜联蛋白A1（ANXA1）是一种钙结合蛋白，在CaCO诱导的肾结石形成过程中，肾细胞顶端表面显著增加。在这方面，我们鉴定了负责钙结合的肽基序，并将其重新设计成自组装肽序列，同时不干扰其对CaCO界面的结合选择性。我们开发了一种盐依赖性策略，通过使用R8肽水溶液和净电荷为 -3的16氨基酸设计肽（WAEEFLKWLAFIEEFF）来制备自组装球形肽纳米颗粒。肽纳米颗粒通过激活Nrf2-HO-1途径恢复了由CaCO晶体（80 µg cm）触发的MDCK细胞的细胞活力并降低了氧化应激。肽纳米颗粒在尿生物化学方面提供了显著保护并减少了钙化，且无任何毒性。
