线粒体IRG1捕捉MCL-1,从而诱导肝细胞亡并促进癌症发生
Liyuan Zhang1, Yue Dong1, Luxin Zhang1
1National Key Laboratory of Medical Immunology & Institute of Immunology, Second Military Medical University, Shanghai, 200433, China.
Cell death & disease
|September 22, 2023
概括
免疫反应基因1 (IRG1) 通过诱导肝细胞亡来促进肝癌. 这一发现揭示了IRG1作为预防肝损伤和肝细胞癌 (HCC) 的潜在治疗点.
科学领域:
- 肝病学 肝病学是一种肝病学.
- 分子生物学分子生物学
- 癌症研究 癌症研究
背景情况:
- 肝癌发生涉及肝细胞死亡和肝损伤,其潜在机制需要进一步调查.
- 众所周知,免疫反应基因1 (IRG1) 和伊塔康酸可调节髓状细胞中的炎症,但它们在肝脏副细胞和肝癌发生中的作用尚不清楚.
研究的目的:
- 调查IRG1在甲胺 (DEN) 诱导的肝癌发生中的作用.
- 阐明IRG1影响肝细胞亡和肝损伤的机制.
主要方法:
- 利用一种甲胺 (DEN) 诱导的肝癌发生的小鼠模型.
- 在DEN给药后,在肝细胞中评估IRG1表达.
- 研究了IRG1介导的亡的分子机制,包括线粒体局部化和蛋白质相互作用.
主要成果:
- 肝细胞IRG1表达显著受到DEN的诱导.
- DEN诱导的IRG1促进了肝细胞的内在线粒体亡,并加剧了肝损伤,从而增强了肝癌发生.
- 发现线粒体IRG1结合MCL-1,抑制其与Bim的相互作用,导致Bim激活,Bax转位和亡启动.
结论:
- 可诱导的线粒体IRG1促进肝细胞亡和随后的肝癌发生.
- IRG1在肝损伤和肝细胞癌 (HCC) 的发展中发挥着关键作用.
- IRG1代表了预防肝损伤和HCC的潜在治疗标.
相关概念视频
Electron Transport Chain: Complex I and II
14.3K
The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
ROS generation is regulated and maintained at moderate levels necessary...
ROS generation is regulated and maintained at moderate levels necessary...
14.3K
The Intrinsic Apoptotic Pathway
6.6K
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...
6.6K
Mutagenicity and Carcinogenicity
1.3K
Mutagenicity and carcinogenicity refer to the ability of drugs to cause genetic defects and induce cancer, respectively. The International Agency for Research on Cancer (IARC) classifies agents into four groups based on their carcinogenic potential. Group 1 agents are known human carcinogens; group 2A agents are probably carcinogenic to humans; group 3 agents lack data to support their role in carcinogenesis; and group 4 includes agents for which data support that they are not likely to be...
1.3K
Regulation of the Unfolded Protein Response
2.5K
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...
2.5K
Abnormal Proliferation
4.6K
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...
4.6K
Induced Pluripotent Stem Cells
4.1K
Stem cells are undifferentiated cells that divide and produce different cell types. Ordinarily, cells that have differentiated into a specific cell type are terminally differentiated; however, scientists have found a way to reprogram these mature cells so that they dedifferentiate and return to an unspecialized, proliferative state. These cells are pluripotent like embryonic stem cells—able to produce all cell types—and are called induced pluripotent stem cells (iPSCs).
Somatic...
Somatic...
4.1K


