Spermidine protects cartilage from IL-1β-mediated ferroptosis.

IF 3.5 2区 生物学 Q3 CELL BIOLOGY
Molecular and Cellular Biochemistry Pub Date : 2024-10-01 Epub Date: 2023-12-02 DOI:10.1007/s11010-023-04889-8
Qi Cheng, Li Ni, Ang Liu, Xiaoxiong Huang, Pan Xiang, Qin Zhang, Huilin Yang
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Abstract

Rheumatoid arthritis is characterized by a burst of inflammation, the destruction of cartilage and the abundant release of inflammatory factors such as IL-1β. Thus, the effect of IL-1β on cartilage was examined in this study. IL-1β could cause lipid peroxidation and disturbances in iron metabolism by increasing the expression of NCOA4 and decreasing the expression of FTH, which also induced ferritinophagy. In addition, the expression of the key antioxidant proteins SLC7A11 and GPX4 was inhibited by IL-1β, resulting in ferroptosis in chondrocytes. Spermidine (SPD), a low-molecular-weight aliphatic nitrogen-containing compound that widely exists in animals, has been reported to be an antioxidant. In our study, we found that SPD could inhibit ferritinophagy and reverse the decrease in the expression of SLC7A11 and GPX4. Therefore, we uncovered one of the molecular mechanisms of cartilage destruction and inflammation and provide a potential polyamine for the treatment of RA.

Abstract Image

亚精胺保护软骨免受il -1β介导的铁下垂。
类风湿关节炎的特点是炎症发作,软骨破坏,炎症因子如IL-1β大量释放。因此,本研究考察了IL-1β对软骨的影响。IL-1β通过增加NCOA4的表达,降低FTH的表达,引起脂质过氧化和铁代谢紊乱,并诱导铁蛋白自噬。此外,关键抗氧化蛋白SLC7A11和GPX4的表达被IL-1β抑制,导致软骨细胞铁下垂。亚精胺(SPD)是一种广泛存在于动物体内的低分子量脂肪族含氮化合物,具有抗氧化剂的作用。在我们的研究中,我们发现SPD可以抑制铁蛋白自噬,逆转SLC7A11和GPX4表达的下降。因此,我们揭示了软骨破坏和炎症的分子机制之一,并为治疗RA提供了一种潜在的多胺。
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来源期刊
Molecular and Cellular Biochemistry
Molecular and Cellular Biochemistry 生物-细胞生物学
CiteScore
8.30
自引率
2.30%
发文量
293
审稿时长
1.7 months
期刊介绍: Molecular and Cellular Biochemistry: An International Journal for Chemical Biology in Health and Disease publishes original research papers and short communications in all areas of the biochemical sciences, emphasizing novel findings relevant to the biochemical basis of cellular function and disease processes, as well as the mechanics of action of hormones and chemical agents. Coverage includes membrane transport, receptor mechanism, immune response, secretory processes, and cytoskeletal function, as well as biochemical structure-function relationships in the cell. In addition to the reports of original research, the journal publishes state of the art reviews. Specific subjects covered by Molecular and Cellular Biochemistry include cellular metabolism, cellular pathophysiology, enzymology, ion transport, lipid biochemistry, membrane biochemistry, molecular biology, nuclear structure and function, and protein chemistry.
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