Table_3_Excessive Inorganic Phosphate Burden Perturbed Intracellular Signaling: Quantitative Proteomics and Phosphoproteomics Analyses.XLSX

Inorganic phosphate (Pi) is an essential nutrient for the human body which exerts adverse health effects in excess and deficit. High Pi-mediated cytotoxicity has been shown to induce systemic organ damage, though the underlying molecular mechanisms are poorly understood. In this study, we employed proteomics and phosphoproteomics to analyze Pi-mediated changes in protein abundance and phosphorylation. Bioinformatic analyses and literature review revealed that the altered proteins and phosphorylation were enriched in signaling pathways and diverse biological processes. Western blot analysis confirms the extensive change in protein level and phosphorylation in key effectors that modulate pre-mRNA alternative splicing. Global proteome and phospho-profiling provide a bird-eye view of excessive Pi-rewired cell signaling networks, which deepens our understanding of the molecular mechanisms of phosphate toxicity.

无机磷酸盐（inorganic phosphate, Pi）是人体必需的营养物质，其过量或缺乏均会对人体健康产生不利影响。已有研究表明，高Pi介导的细胞毒性可引发全身性器官损伤，但其背后的分子机制尚不明晰。本研究采用蛋白质组学（proteomics）与磷酸化蛋白质组学（phosphoproteomics）技术，分析Pi介导的蛋白质丰度与磷酸化修饰水平的变化。生物信息学分析与文献综述结果显示，差异表达蛋白质及磷酸化修饰位点显著富集于多条信号通路与多种生物学过程中。蛋白质印迹法（Western blot）分析证实，调控前体信使RNA（pre-mRNA）可变剪接的关键效应分子的蛋白质水平与磷酸化状态均发生广泛改变。全局蛋白质组与磷酸化谱分析可为过量Pi重编程的细胞信号网络提供全景式概览，从而加深我们对磷酸盐毒性分子机制的理解。