Multifunctions of Sustainable Chondroitin Sulfates with Predominant Subtypes and Low Molecular Weights on Neurite Outgrowth.

IF 5.5 2区化学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biomacromolecules Pub Date : 2025-01-21 DOI:10.1021/acs.biomac.4c01713

Shuqin Xu, Meiling Qiu, Liyuan Liang, Yue Chen, Yajia Wang, Jing Wu, Jinghua Chen

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引用次数: 0

Abstract

Three chondroitin sulfate (CS) analogues with predominant subtypes (A, C, and E) were prepared from engineered Escherichia coli K4 combined with regioselective sulfation. CS with the designed sulfates as the main components was characterized by nuclear magnetic resonance spectroscopy, elementary analysis, and disaccharide analysis. CS prepared from the native or degraded capsular polysaccharide had molecular weights of 1.55 × 10⁴-1.90 × 10⁴ and 5.6 × 10³-7.4 × 10³, respectively. We found that CS with dual sulfates promoted the outgrowth and survival of hippocampal neurons, whereas CS with monosulfate had an inhibitory effect. CS interacted with the nerve growth factor (NGF) and tyrosine kinase (TrkA), which activated the extracellular signal-regulated kinase (ERK) signaling pathway to modulate the outgrowth of hippocampal neurons. This work clarified the multiple effects of CS on neurite outgrowth based on nonanimal-sourced glycosaminoglycans, which would benefit efforts in discovering their novel functions and therapeutic applications.

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具有优势亚型和低分子量的可持续硫酸软骨素对神经突生长的多功能作用。

利用工程大肠杆菌K4结合区域选择性磺化法制备了3种主要亚型（A、C和E）硫酸软骨素（CS）类似物。用核磁共振谱、元素分析和双糖分析对设计的硫酸盐为主要成分的CS进行了表征。由天然荚膜多糖和降解荚膜多糖制备的CS分子量分别为1.55 × 104 ~ 1.90 × 104和5.6 × 103 ~ 7.4 × 103。我们发现，双硫酸盐CS促进海马神经元的生长和存活，而单硫酸盐CS具有抑制作用。CS与神经生长因子（NGF）和酪氨酸激酶（TrkA）相互作用，激活细胞外信号调节激酶（ERK）信号通路，调节海马神经元的生长。本研究阐明了CS对基于非动物源糖胺聚糖的神经突生长的多重影响，这将有助于发现其新功能和治疗应用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Biomacromolecules 化学-高分子科学

CiteScore

10.60

自引率

4.80%

发文量

417

审稿时长

1.6 months

期刊介绍： Biomacromolecules is a leading forum for the dissemination of cutting-edge research at the interface of polymer science and biology. Submissions to Biomacromolecules should contain strong elements of innovation in terms of macromolecular design, synthesis and characterization, or in the application of polymer materials to biology and medicine. Topics covered by Biomacromolecules include, but are not exclusively limited to: sustainable polymers, polymers based on natural and renewable resources, degradable polymers, polymer conjugates, polymeric drugs, polymers in biocatalysis, biomacromolecular assembly, biomimetic polymers, polymer-biomineral hybrids, biomimetic-polymer processing, polymer recycling, bioactive polymer surfaces, original polymer design for biomedical applications such as immunotherapy, drug delivery, gene delivery, antimicrobial applications, diagnostic imaging and biosensing, polymers in tissue engineering and regenerative medicine, polymeric scaffolds and hydrogels for cell culture and delivery.