Martucci Luiz Felipe, Eichler Rosangela A S, Silva Renée N O, Costa Tiago J, Tostes Rita C, Busatto Geraldo F, Seelaender Marilia C L, Duarte Alberto J S, Souza Heraldo P, Ferro Emer S
Department of Pharmacology, Biomedical Sciences Institute, São Paulo 05508-000, Brazil.
Department of Pharmacology, Ribeirao Preto Medical School, Ribeirão Preto 14049-900, Brazil.
iScience. 2023 Aug 6;26(9):107542. doi: 10.1016/j.isci.2023.107542. eCollection 2023 Sep 15.
Intracellular peptides (InPeps) generated by the orchestrated action of the proteasome and intracellular peptidases have biological and pharmacological significance. Here, human plasma relative concentration of specific InPeps was compared between 175 patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and 45 SARS-CoV-2 non-infected patients; 2,466 unique peptides were identified, of which 67% were InPeps. The results revealed differences of a specific group of peptides in human plasma comparing non-infected individuals to patients infected by SARS-CoV-2, following the results of the semi-quantitative analyses by isotope-labeled electrospray mass spectrometry. The protein-protein interactions networks enriched pathways, drawn by genes encoding the proteins from which the peptides originated, revealed the presence of the coronavirus disease/COVID-19 network solely in the group of patients fatally infected by SARS-CoV-2. Thus, modulation of the relative plasma levels of specific InPeps could be employed as a predictive tool for disease outcome.
蛋白酶体和细胞内肽酶协同作用产生的细胞内肽（InPeps）具有生物学和药理学意义。在此，比较了175例感染严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的患者与45例未感染SARS-CoV-2的患者之间特定InPeps的人血浆相对浓度；鉴定出2466种独特的肽，其中67%为InPeps。同位素标记电喷雾质谱半定量分析结果显示，与未感染个体相比，感染SARS-CoV-2的患者血浆中特定肽组存在差异。由编码肽来源蛋白质的基因绘制的蛋白质-蛋白质相互作用网络富集途径显示，仅在致命感染SARS-CoV-2的患者组中存在冠状病毒病/COVID-19网络。因此，特定InPeps相对血浆水平的调节可作为疾病预后的预测工具。
