通过调节GPX4蛋白的稳定性,P21抵抗骨关节性肌肉细胞中的铁亡
Zehang Zheng1, Xingru Shang2, Kai Sun1
1Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Free radical biology & medicine
|January 4, 2024
概括
作为衰老指标的P21,通过抑制铁亡,可以预防骨关节炎 (OA). 这项研究表明,P21稳定GPX4,对于预防OA细胞死亡和软骨损伤至关重要.
科学领域:
- 生物化学 生物化学
- 细胞生物学 细胞生物学
- 病理学 病理学 病理学
背景情况:
- 铁致死有助于骨关节炎 (OA) 的发病.
- 抑制冠状细胞铁致死有益于OA.
- P21的作用,一个衰老指标,在OA铁死是不清楚的.
研究的目的:
- 研究OA胆固醇细胞中的P21表达和功能.
- 阐明P21在调节冠状细胞铁亡中的作用.
- 确定P21在OA铁亡中的机制.
主要方法:
- 评估了OA患者软骨,DMM小鼠和IL-1β/FAC/erastin诱导的红细胞中的P21表达.
- 在体外和体内进行了P21的淘汰.
- 分析了GPX4蛋白稳定性,脂质过氧化物积累和GPX4无处不在.
主要成果:
- 在OA软骨和软骨细胞中观察到高P21表达.
- 在P21中,OA表型恶化,Col2a1减少,MMP13增加,软骨退化恶化.
- P21 knockdown 对铁细胞敏感,与减少GPX4和增加脂质过氧化物有关.
结论:
- 在OA中,P21作为抗费洛症因子起作用.
- P21通过独立于NRF2.2的LUBAC介导的M1结合的全方位化调节GPX4蛋白的稳定性.
- 准P21可能为OA提供治疗策略.
关键词:
(Bortezomib,PubChem CID: 387447) 这是一款药物.(PubChem CID: 11214940) 这是一个非常重要的数字.(Tert-Butylhydroquinone,PubChem CID: 16043) 这种药物可以在任何药物中使用.(Z-Leu-leu-leu-al,PubChem CID: 462382) 这是一个非常重要的数字.(循环赫西米德,PubChem CID: 6197) 这种药物可以(铁氨酸盐,PubChem CID: 14457) 这是一种铁酸盐.CHX CHX 在这里埃拉斯廷就是这样.在FAC中,FAC是FAC.铁化是铁化的一种.在GPX4中使用GPX4.与M1相关的无处不在化.MG132 MG132 MG132 MG132 MG132 MG132 MG132 MG132 MG132 MG132 MG132 MG132 MG132 MG132 MG132 MG132 MG132 MG132 MG132 MG132 MG132 MG132 MG132骨关节炎是一种骨关节炎.在P2121中,P21是指P21.PS341 这是一本书.在TBHQQ中,相关概念视频
Regulation of the Unfolded Protein Response
2.4K
Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
2.4K
Abnormal Proliferation
4.5K
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.5K
The Unfolded Protein Response
4.6K
The ER is the hub of protein synthesis in a cell. It has robust systems to quality control protein folding and also for degradation of terminally misfolded proteins. Under normal conditions, a small proportion of misfolded proteins that cannot be salvaged need to be transported to the cytoplasm by the ER-associated degradation or ERAD pathways. However, if the ERAD cannot handle the misfolded proteins, the cell activates the unfolded protein response or UPR to adjust the protein folding...
4.6K
Necrosis
4.5K
Necrosis is considered as an “accidental” or unexpected form of cell death that ends in cell lysis. The first noticeable mention of “necrosis” was in 1859 when Rudolf Virchow used this term to describe advanced tissue breakdown in his compilation titled “Cell Pathology”.
Morphological Manifestations of Necrosis
Necrotic cells show different types of morphological appearance depending on the type of tissue and infection. In coagulative necrosis, cells become...
Morphological Manifestations of Necrosis
Necrotic cells show different types of morphological appearance depending on the type of tissue and infection. In coagulative necrosis, cells become...
4.5K
Export of Misfolded Proteins out of the ER
3.6K
After folding, the ER assesses the quality of secretory and membrane proteins. The correctly folded proteins are cleared by the calnexin cycle for transport to their final destination, while misfolded proteins are held back in the ER lumen. The ER chaperones attempt to unfold and refold the misfolded proteins but sometimes fail to achieve the correct native conformation. Such terminally misfolded proteins are then exported to the cytosol by ER-associated degradation or ERAD pathway for...
3.6K
Regulated Protein Degradation
7.3K
It is vital to regulate the activity of enzymatic as well as non-enzymatic proteins inside the cell. This can be achieved either through creating a balance between their rate of synthesis and degradation or regulating the intrinsic activity of the protein. Both these regulation mechanisms play an essential role in the normal functioning of cells.
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
7.3K


