奥图林编排NCOA4-FTH1复合体以缓解APAP诱导的肝细胞铁亡
Liyuan Gao1, Xiaoyan Chang1, Yi Han1
1Zhangjiagang TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Suzhou, China.
International immunopharmacology
|March 30, 2025
概括
过量服用乙氨基会通过促进细胞死亡通路ferroptosis引起肝损伤. 升级的OTULIN保护肝细胞免受这种损伤,为乙氨基诱导的肝损伤提供了潜在的治疗方法.
科学领域:
- 肝病学 肝病学是一种肝病学.
- 细胞死亡机制 细胞死亡机制
- 药物诱导的肝损伤
背景情况:
- 乙氨基 (APAP) 过量服用是药物诱导的肝损伤 (DILI) 和急性肝衰竭 (ALF) 的主要原因.
- 肝细胞死亡是APAP毒性的核心,但机制尚不清楚.
- 铁,一种涉及铁和谷氨的细胞死亡形式,与APAP肝毒性具有共同的特征.
研究的目的:
- 研究ferroptosis在APAP诱导的肝损伤中的作用.
- 确定APAP诱导的DILI的治疗点.
主要方法:
- 给C57BL/6小鼠服用APAP,用于体内评估铁亡和肝损伤.
- 在体外机理学研究中利用分子技术和稳定细胞系.
主要成果:
- APAP破坏铁的稳态,诱导肝细胞铁亡.
- 奥图林二维基因酶调节NCOA4的泛基因化,导致NCOA4的耗尽和FTH1的积累.
- 这种调节增强了肝细胞对APAP诱导的损伤的抵抗力.
结论:
- 奥图林通过NCOA4-FTH1复合体保护APAP诱导的肝细胞铁亡.
- 在肝细胞中有针对性的OTULIN上调显示了APAP-DILI的治疗潜力.
相关概念视频
The Electron Transport Chain
The electron transport chain or oxidative phosphorylation is an exothermic process in which free energy released during electron transfer reactions is coupled to ATP synthesis. This process is a significant source of energy in aerobic cells, and therefore inhibitors of the electron transport chain can be detrimental to the cell's metabolic processes.
Inhibitors of the electron transport chain
Rotenone, a widely used pesticide, prevents electron transfer from Fe-S cluster to ubiquinone or Q in...
Inhibitors of the electron transport chain
Rotenone, a widely used pesticide, prevents electron transfer from Fe-S cluster to ubiquinone or Q in...
Allosteric Proteins-ATCase
Binding sites linkages can regulate a protein's function. For example, enzyme activity is often regulated through a feedback mechanism where the end product of the biochemical process serves as an inhibitor.
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis pathway,...
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis pathway,...
The Extrinsic Apoptotic Pathway
The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
The Intrinsic Apoptotic Pathway
Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
Necrosis
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 anucleated and die, but their...
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 anucleated and die, but their...

