关键词: Fluorescent imaging Fluorescent sensor Peripheral neuropathy Protein aggregation Proteomics

Mesh : Peripheral Nervous System Diseases / chemically induced metabolism Humans Proteome / analysis metabolism Antineoplastic Agents / pharmacology chemistry Molecular Structure Protein Aggregates / drug effects Optical Imaging Dose-Response Relationship, Drug Proteomics Fluorescent Dyes / chemistry pharmacology

来  源:   DOI:10.1016/j.bioorg.2024.107491

Abstract:
As a consequence of somatosensory nervous system injury or disease, neuropathic pain is commonly associated with chemotherapies, known as chemotherapy-induced peripheral neuropathy (CIPN). However, the mechanisms underlying CIPN-induced proteome aggregation in neuronal cells remain elusive due to limited detection tools. Herein, we present series sensors for fluorescence imaging (AggStain) and proteomics analysis (AggLink) to visualize and capture aggregated proteome in CIPN neuronal cell model. The environment-sensitive AggStain imaging sensor selectively binds and detects protein aggregation with 12.3 fold fluorescence enhancement. Further, the covalent AggLink proteomic sensor captures cellular aggregated proteins and profiles their composition via LC-MS/MS analysis. This integrative sensor platform reveals the presence of proteome aggregation in CIPN cell model and highlights its potential for broader applications in assessing proteome stability under various cellular stress conditions.
摘要:
由于体感神经系统损伤或疾病,神经性疼痛通常与化疗有关,称为化疗引起的周围神经病变(CIPN)。然而,由于检测手段有限,CIPN诱导的神经元细胞蛋白质组聚集的机制仍然难以捉摸.在这里,我们提供了用于荧光成像(AggStain)和蛋白质组学分析(AggLink)的系列传感器,以可视化和捕获CIPN神经元细胞模型中聚集的蛋白质组。环境敏感的AggStain成像传感器选择性结合并检测具有12.3倍荧光增强的蛋白质聚集。Further,共价AggLink蛋白质组传感器通过LC-MS/MS分析捕获细胞聚集的蛋白质并描述其组成。该集成传感器平台揭示了CIPN细胞模型中蛋白质组聚集的存在,并强调了其在各种细胞应激条件下评估蛋白质组稳定性的更广泛应用的潜力。
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