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Amyloid like Aggregates Formed by the Self-Assembly of Proline and Hydroxyproline
ChemRxiv Pub Date : 2021-01-21
Bharti Koshti, Ramesh, Singh, Vivekshinh Kshtriya, Shanka Walia, Dhiraj Bhatia, khashti Ballabh Joshi, Nidhi Gour

Single amino acid based self-assembled structures have gained a lot of interest recently owing to their pathological significance in metabolite disorders. There is plethora of significant research work which illustrate amyloid like characteristics of assemblies formed by aggregation of single amino acids like Phenylalanine, Tyrosine, Tryptophan, Cysteine and Methionine and its implications in pathophysiology of single amino acid metabolic disorders like phenylketonuria, tyrosinemia, hypertryptophanemia, cystinuria and hypermethioninemia respectively. Hence, studying aggregation behaviour of single amino acids is very crucial to assess the underlying molecular mechanism behind metabolic disorders. In this manuscript we report for the very first time the aggregation properties of non-aromatic single amino acids Hydroxy-proline and Proline. The morphologies of these were studied extensively by Optical microscopy (OM), ThT binding fluorescence microscopy, Scanning Electron Microscopy (SEM) and Atomic force microscopy (AFM). It can be assessed that these amino acids form globular structures at lower concentrations and gradually changes to tape like structures on increasing the concentration as assessed by AFM. ThT and CR binding assay reveal the aggregates do have amyloid like characteristics. Further MTT assays on SHSY5Y neural cell lines reveal cytotoxicity and the aggregates caused significant cell death in dose dependent manner. These results have important implications in understanding the pathophysiology of single amino acid disorders like Hyperprolinemia and Hydroxyprolinemia in association with amyloid diseases. The symptoms of these diseases are also accompanied by extensive neurological problems like intellectual disability, seizures and psychiatric problems which further evince amyloid like etiology for these rare in-born errors of metabolism.

中文翻译:

脯氨酸和羟脯氨酸自组装形成的淀粉样聚集体

基于单氨基酸的自组装结构由于其在代谢物疾病中的病理学意义而最近引起了很多兴趣。大量的大量研究工作阐明了由单个氨基酸(如苯丙氨酸,酪氨酸,色氨酸,半胱氨酸和蛋氨酸)的聚集形成的组装体的淀粉样蛋白样特征,及其对单氨基酸代谢紊乱(如苯丙酮尿症,酪氨酸血症,高色氨酸血症,胱氨酸尿症)的病理生理学的影响。和高蛋氨酸血症。因此,研究单个氨基酸的聚集行为对于评估代谢紊乱背后的潜在分子机制非常重要。在此手稿中,我们首次报告了非芳香族单氨基酸羟基脯氨酸和脯氨酸的聚集特性。通过光学显微镜(OM),ThT结合荧光显微镜,扫描电子显微镜(SEM)和原子力显微镜(AFM)广泛研究了它们的形态。可以评估这些氨基酸在较低浓度下形成球状结构,并随着浓度的增加而逐渐改变为带状结构,如AFM所评估的。ThT和CR结合测定揭示了聚集体确实具有淀粉样样特征。在SHSY5Y神经细胞系上进行的进一步MTT分析显示出细胞毒性,并且聚集体以剂量依赖性方式引起了明显的细胞死亡。这些结果对于理解单个氨基酸疾病(如高蛋白血症和羟脯氨酸血症)与淀粉样蛋白疾病有关的病理生理学具有重要意义。
更新日期:2021-01-21
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