Biological Mass Spectrometry and Proteomics Group, SMBP, PDC CNRS UMR, 8249, ESPCI Paris, Université PSL, 10 rue Vauquelin, 75005, Paris, France.
Department of Experimental and Clinical Biomedical Sciences, University of Florence, Viale G.B. Morgagni 50, 50134, Florence, Italy.
Redox Biol. 2022 Jun;52:102294. doi: 10.1016/j.redox.2022.102294. Epub 2022 Mar 22.
The effects of Auranofin (AF) on protein expression and protein oxidation in A2780 cancer cells were investigated through a strategy based on simultaneous expression proteomics and redox proteomics determinations. Bioinformatics analysis of the proteomics data supports the view that the most critical cellular changes elicited by AF treatment consist of thioredoxin reductase inhibition, alteration of the cell redox state, impairment of the mitochondrial functions, metabolic changes associated with conversion to a glycolytic phenotype, induction of ER stress. The occurrence of the above cellular changes was extensively validated by performing direct biochemical assays. Our data are consistent with the concept that AF produces its effects through a multitarget mechanism that mainly affects the redox metabolism and the mitochondrial functions and results into severe ER stress. Results are discussed in the context of the current mechanistic knowledge existing on AF.
通过基于同时表达蛋白质组学和氧化还原蛋白质组学测定的策略，研究了金诺芬（AF）对 A2780 癌细胞中蛋白质表达和蛋白质氧化的影响。蛋白质组学数据的生物信息学分析支持这样的观点，即 AF 处理引起的最关键的细胞变化包括硫氧还蛋白还原酶抑制、细胞氧化还原状态改变、线粒体功能障碍、与糖酵解表型转换相关的代谢变化、内质网应激诱导。通过直接生化测定广泛验证了上述细胞变化的发生。我们的数据与 AF 通过多靶点机制产生作用的概念一致，该机制主要影响氧化还原代谢和线粒体功能，并导致严重的内质网应激。结果在现有的关于 AF 的机制知识背景下进行了讨论。
