State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products, Ningbo University, Ningbo, Zhejiang 315211, China; School of Marine Sciences, Ningbo University, Ningbo, Zhejiang 315832, China.
State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products, Ningbo University, Ningbo, Zhejiang 315211, China; College of Food and Pharmaceutical Sciences, Ningbo University, Ningbo, Zhejiang 315832, China.
Ecotoxicol Environ Saf. 2021 Apr 1;212:111995. doi: 10.1016/j.ecoenv.2021.111995. Epub 2021 Jan 30.
Ferritin is the major intracellular iron storage protein and is essential for iron homeostasis and detoxification. Cadmium affects cellular homeostasis and induces cell toxicity via sophisticated mechanisms. Here, we aimed to explore the mechanisms of cytoprotective effect of Phascolosoma esculenta ferritin (PeFer) on Cd(II)-induced bone marrow mesenchymal stem cell (BMSC) injury. Herein, the effects of different treated groups on apoptosis and cell cycle were assessed using flow cytometric analysis. We further investigated the alterations of the three groups using integrative 2-DE-based proteomics and H NMR-based metabolomics profiles. The results indicate that PeFer reduces BMSC apoptosis induced by Cd(II) and delays G0/G1 cell cycle progression. A total of 19 proteins and 70 metabolites were significantly different among BMSC samples of the three groups. Notably, multiomics analysis revealed that Cd(II) might perturb the ER stress-mediated apoptosis pathway and disrupt biological processes related to the TCA cycle, amino acid metabolism, purine and pyrimidine metabolism, thereby suppressing the cell growth rate and initiating apoptosis; however, the addition of PeFer might protect BMSCs against cell apoptosis to improve cell survival by enhancing energy metabolism. This study provides a better understanding of the underlying molecular mechanisms of the protective effect of PeFer in BMSCs against Cd(II) injury.
铁蛋白是主要的细胞内铁储存蛋白，对于铁稳态和解毒至关重要。镉通过复杂的机制影响细胞内稳态并诱导细胞毒性。在这里，我们旨在探索 Phascolosoma esculenta 铁蛋白 (PeFer) 对 Cd(II)诱导的骨髓间充质干细胞 (BMSC) 损伤的保护作用的机制。在此，使用流式细胞术分析评估了不同处理组对细胞凋亡和细胞周期的影响。我们进一步使用整合的基于 2-DE 的蛋白质组学和基于 H NMR 的代谢组学图谱研究了三组的变化。结果表明，PeFer 可减少 Cd(II)诱导的 BMSC 凋亡并延缓 G0/G1 细胞周期进程。三组 BMSC 样本之间共有 19 种蛋白质和 70 种代谢物存在显著差异。值得注意的是，多组学分析表明，Cd(II)可能会扰乱 ER 应激介导的细胞凋亡途径，并破坏与 TCA 循环、氨基酸代谢、嘌呤和嘧啶代谢相关的生物过程，从而抑制细胞生长速率并引发细胞凋亡；然而，添加 PeFer 可能通过增强能量代谢来保护 BMSC 免受细胞凋亡，从而提高细胞存活率。本研究为 PeFer 对 BMSC 对抗 Cd(II)损伤的保护作用的潜在分子机制提供了更好的理解。
