无形的二氧化纳米颗粒通过中枢复合体和微纤维的功能障碍引起异常的细胞动力学和多核化
Liyan Xiao1, Jinyan Pang1, Hua Qin1,2
1Beijing Key Laboratory of Environmental Toxicology, School of Public Health, Capital Medical University, Beijing, 100069, P.R. China.
Particle and fibre toxicology
|August 23, 2023
概括
无形二氧化纳米粒子 (aSiNPs) 通过破坏细胞分裂,导致肝脏和肺组织的多核化. 这通过增加ROS发生,抑制PI3k/Aurora B通路,并损害参与细胞动因的关键蛋白质.
科学领域:
- 纳米技术纳米技术
- 毒理学 毒理学 毒理学
- 细胞生物学 细胞生物学
背景情况:
- 无形纳米粒子 (aSiNPs) 的大规模生产和使用需要了解它们对健康的影响.
- 之前的研究发现aSiNPs在体外诱导细胞因子失败和多核化.
- aSiNPs诱导的多核化的潜在机制仍然不清楚.
研究的目的:
- 为了确定aSiNPs是否在体内诱导多核化.
- 研究aSiNPs引起异常细胞动力学和多核化的机制.
主要方法:
- 在雄性ICR小鼠中对aSiNPs进行内灌注,用于体内研究.
- 利用人类肝细胞系 (L-02) 进行体外机理学研究.
- 采用了组织病理学,免疫光学和分子通路分析.
主要成果:
- 在暴露于aSiNP的小鼠的肝脏和肺组织中,多核化率显著增加.
- aSiNPs诱导了微纤维聚合和高反应性氧物种 (ROS) 在体外的水平.
- 通过ROS抑制PI3k 110β/Aurora B通路导致中枢旋子单元和细胞动力学相关蛋白质的表达减少,最终导致细胞动力学失败.
结论:
- aSiNP在体内和体外都会诱导多核化.
- 暴露于aSiNPs会触发微纤维聚合,并通过过度的ROS抑制PI3k 110β/Aurora B通路.
- 这种途径的抑制阻碍了中央链复合体的形成,并降低了必需的细胞动力学蛋白质的调节,导致细胞分裂失败和多核化.
相关概念视频
01:39Mechanism of Filopodia Formation
2.4K
Filopodia are thin, actin-rich cellular protrusions that play an important role in many fundamental cellular functions. They vary in their occurrence, length, and positioning in different cell types, suggesting their diverse roles.
Their main function is to guide migrating cells during normal tissue morphogenesis or cancer metastasis by recognizing and making initial contacts with the extracellular matrix. However, they can also act as stationary cell anchors or help to establish communication...
Their main function is to guide migrating cells during normal tissue morphogenesis or cancer metastasis by recognizing and making initial contacts with the extracellular matrix. However, they can also act as stationary cell anchors or help to establish communication...
2.4K
01:45Destabilization of Microtubules
2.8K
The destabilization of microtubules can occur during different stages of the microtubule lifecycle, such as nucleation or elongation. It can take place at either end of the microtubule or in the microtubule lattices as a whole. The lifespan of individual microtubules within a cell varies according to the cell type and stage of the cell cycle. During interphase, the lifespan of the microtubule is about 30 minutes, while during cell division, it is about 15 minutes. In axonal microtubules of...
2.8K
02:17Microtubule Instability
5.2K
Microtubules are hollow cylindrical filaments having a diameter of approximately 25 nm and a length that varies from 200 nm to 25 μm. GTP-bound tubulin subunits form αβ-heterodimers for microtubule assembly. These core building blocks interact longitudinally, polymerizing into protofilaments. The protofilaments then interact with one another through lateral bonding forces to form stable cylindrical microtubules. These cylindrical filaments are dynamic as they undergo repeated...
5.2K
01:35Disassembly of Intermediate Filaments
2.1K
Intermediate filaments (IFs) do not undergo spontaneous disassembly. Enzymes, kinases, and phosphatases add and remove phosphates from specific sites to regulate their disassembly. The IF concentration in the cytoplasm also regulates the disassembly. If the concentration crosses a threshold, it activates the protein kinases in the vicinity, allowing the phosphorylation of IFs.
Keratin proteins, found at the cell periphery near cell junctions, undergo a cycle of assembly and disassembly. In Type...
Keratin proteins, found at the cell periphery near cell junctions, undergo a cycle of assembly and disassembly. In Type...
2.1K
02:50Spindle Assembly
3.7K
Spindle assembly occurs through three, often coexisting, pathways – the centrosome-mediated pathway, the chromatin-mediated pathway, and the microtubule-mediated pathway – collectively contributing to form a robust spindle apparatus.
In most cells, centrosomes are the primary microtubule nucleation centers. In the centrosome-mediated pathway, the G2-prophase transition triggers centrosome maturation and increased microtubule nucleation. Progressive nucleation results in a...
In most cells, centrosomes are the primary microtubule nucleation centers. In the centrosome-mediated pathway, the G2-prophase transition triggers centrosome maturation and increased microtubule nucleation. Progressive nucleation results in a...
3.7K
01:12Adaptability of Cytoskeletal Filaments
3.8K
The cytoskeleton is a complex dynamic structure performing varied functions based on cellular requirements. The adaptability of the individual filaments in the cytoskeleton determines their ability to perform various functions within the cell. It can undergo rapid reorganization during processes like cell division or remain stable for several hours as in the interphase. The adaptability of these filaments depends on stringent regulatory mechanisms. The microfilament and microtubules of the...
3.8K