脱氧尼瓦伦醇通过提高氧化应激诱导DRP-1介导的线粒体功能障碍
Sakshi Mishra1, Radhika Kapoor1, Sushma1
1Genotoxicity Laboratory, Division of Toxicology and Experimental Medicine, CSIR-Central Drug Research Institute, Lucknow 226031, Uttar Pradesh, India.
Chemical research in toxicology
|June 14, 2024
概括
脱氧尼瓦伦醇 (DON) 菌毒素暴露会增加神经元细胞中的氧化应激,水平和线粒体裂变,导致细胞死亡. 抑制ROS和线粒体分裂可能为神经退行性疾病提供治疗策略.
科学领域:
- 神经科学是一个神经科学.
- 毒理学 毒理学 毒理学
- 细胞生物学 细胞生物学
背景情况:
- 线粒体功能障碍和氧化压力与神经毒性和神经系统疾病有关.
- 脱氧尼瓦伦醇 (DON) 是一种常见的真菌毒素,会污染食品和料,造成健康风险.
- 将DON与神经退行性疾病联系起来的全面研究是有限的.
研究的目的:
- 研究DON在线粒体动力学和神经元细胞中细胞死亡中的作用.
- 阐明DON诱导的神经毒性的机制.
- 探索毒素诱导的神经退行症的潜在治疗点.
主要方法:
- 人类SH-SY5Y神经细胞被用不同度的DON治疗.
- 评估了反应性氧物种 (ROS) 的产生,ATP水平,线粒体膜潜力,水平和细胞毒性.
- 分析了线粒体裂变/融合蛋白 (P-Drp-1,Mff,Fis-1,MFN1,MFN2,OPA1) 和自标记物的表达 (LC3,beclin-1).
主要成果:
- DON暴露剂量取决于细胞毒性,ROS和细胞内的增加.
- DON治疗降低了ATP水平和线粒体膜潜力.
- DON提高了线粒体分裂蛋白 (P-Drp-1,Mff,Fis-1) 和自标记物,同时降低了融合蛋白 (MFN1,MFN2,OPA1).
- 证实ROS和Ca2+信号通路能够调解DON诱导的Drp1酸化.
结论:
- DON通过增加氧化应激和过度的线粒体裂变,诱导神经元细胞中的线粒体功能障碍和细胞死亡.
- ROS和信号传递是DON神经毒性作用的关键媒介.
- ROS和线粒体裂变的抑制剂为毒素诱导的神经退行性疾病提供了潜在的治疗途径.
相关概念视频
Necrosis
4.4K
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...
4.4K
The Electron Transport Chain
16.5K
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...
Inhibitors of the electron transport chain
Rotenone, a widely used pesticide, prevents electron transfer from Fe-S cluster to ubiquinone or Q...
16.5K
The Unfolded Protein Response
4.5K
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...
4.5K
Electron Transport Chain: Complex I and II
12.9K
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...
12.9K
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
Translocation of Proteins into the Mitochondria
3.1K
Mitochondrial precursors are translocated to the internal subcompartments via independent mechanisms involving distinct protein machineries called translocases.
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
3.1K


