在乙胺诱导的肝损伤中,通过FDX1向cuproptosis
Yan Liu1, Ying Yang2, Baizhao Peng2
1The Affiliated Traditional Chinese Medicine Hospital, Guangzhou Medical University, Guangzhou, Guangdong, 510180, China; Department of Traditional Chinese Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, China; School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, 510515, China.
Chemico-biological interactions
|September 23, 2025
概括
乙氨基过量服用会通过亡,由铁素1 (FDX1) 调节的细胞死亡途径引起肝损伤. 准铜水平可能为药物诱导性肝损伤 (DILI) 提供新的治疗方法.
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
- 毒理学 毒理学 毒理学
背景情况:
- 乙氨基 (APAP) 过量服用是导致药物诱导性肝损伤 (DILI) 的主要原因.
- 虽然氧化应激,亡和亡是已知的机制,但亡在APAP肝毒性中的作用尚不清楚.
- 型亡是一种新发现的,依赖于铜的受调细胞死亡形式.
研究的目的:
- 研究cuproptosis对APAP诱导的肝损伤的贡献.
- 在APAP过量服用的背景下,确定cuproptosis的关键调节者.
- 探索铜恒温作为DILI的潜在治疗点.
主要方法:
- 在APAP治疗小鼠中的体内研究使用铜化剂氨四基酸 (TM).
- 从暴露于APAP的肝细胞中转录基因分析GEO数据集.
- 在小鼠和人类的HepaRG细胞中对铁素1 (FDX1) 进行基因操纵 (切除/敲除).
主要成果:
- 氨四聚酸盐 (TM) 显著降低了APAP诱导的肝损伤,包括较低的ALT/AST水平,肝细胞死亡和炎症.
- 转录组分析揭示了cuproptosis基因的显著失调,FDX1在暴露于APAP的肝细胞中高度上调.
- 保护FDX1基因切除或淘汰,防止APAP诱导的致死性,模仿TM的保护作用.
结论:
- 通过FDX1介导的cuproptosis是推动APAP肝毒性的关键机制.
- 铜平衡是一种有前途的治疗点,用于管理DILI.
- 准FDX1和铜代谢可能为治疗乙氨基过量治疗提供新的策略.
相关概念视频
01:17The 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...
01:12GPCR Desensitization
G protein-coupled receptor (GPCR) signaling plays a crucial role in cell functioning. GPCR desensitization is an equally essential process. It allows cells to respond to changing environments and regain sensitivity to new stimuli while preventing unnecessary stimulation when no longer needed. Prolonged exposure to stimuli leads to GPCR desensitization. It involves blocking the receptors from binding and activating additional G proteins. This inhibits activation of downstream effectors, thereby...
01:24Liver Regeneration
The liver is an important organ in vertebrates that plays an essential role in metabolism. It is also responsible for storing and redistributing nutrients such as carbohydrates, fats, and vitamins in the body. Additionally, the liver releases bile salts which are critical for digesting food and eliminating toxic metabolites from the body.
Cells of Liver
The liver comprises four major types of cells— hepatocytes, stellate, Kupffer, and sinusoidal endothelial cells. The hepatocytes are large...
Cells of Liver
The liver comprises four major types of cells— hepatocytes, stellate, Kupffer, and sinusoidal endothelial cells. The hepatocytes are large...
01:22Cellular Injury V: Apoptosis and Autophagy
Cells respond to damage and stress through highly coordinated processes that decide whether they survive or undergo controlled self-destruction. Two major pathways involved in this regulation are apoptosis, a type of programmed cell death, and autophagy, a survival mechanism that helps cells adapt to adverse conditions.ApoptosisApoptosis removes aged or injured cells to maintain tissue balance. During this process, the cell shrinks, chromatin condenses and fragments, and membrane-bound...
01:24Cirrhosis II: Pathophysiology
Cirrhosis is a progressive chronic liver injury caused by prolonged inflammation, excessive fibrotic remodeling, and impaired regeneration. Over time, repeated hepatic insults disrupt the liver’s architecture and function, leading to reduced blood flow, impaired bile drainage, and diminished metabolic capacity.Pathophysiology of cirrhosisCirrhosis arises from three main responses to chronic liver damage: inflammation, immune activation, and hepatocyte death. These processes lead to structural...