perfluorooctane 硫酸盐会通过铁和内质网膜应激通路引起HK-2细胞损伤
Shuqi Yan1, Haoyan Ma1, Yuwan Ren1
1Department of Occupational and Environmental Health, School of Public Health, Jilin University, Changchun, China.
Toxicology and industrial health
|November 19, 2024
概括
perfluorooctane sulfonate (PFOS) 通过诱导 ferroptosis 和人体近接管状细胞中的内 плазма网膜应激引起损伤. 这项研究揭示了PFOS毒性的机制.
科学领域:
- 毒理学 毒理学 毒理学
- 细胞生物学 细胞生物学
- 环境健康 环境健康
背景情况:
- perfluorooctane sulfonate (PFOS) 是一种具有广泛工业用途的持久性有机污染物.
- PFOS在环境中积累,对人类健康构成风险,特别影响脏,这是主要的排泄途径.
- 了解PFOS引起的损伤对于评估其整体毒性至关重要.
研究的目的:
- 研究PFOS在人类近端管状上皮细胞 (HK-2) 中诱导毒性的机制.
- 为了检查铁亡和内细胞网膜应激 (ERS) 在PFOS介导的细胞损伤中的作用.
主要方法:
- HK-2细胞暴露于PFOS (200微米) 或Fer-1 (1微米).
- 评估了细胞活力,麦隆迪阿尔代海德 (MDA),谷氨酸 (GSH),细胞内铁和谷氨酸过氧化酶4 (GPX-4) 的水平.
- 测量损伤分子-1 (KIM-1) 和与ERS相关的蛋白质 (GRP78,ATF6,IRE1,PERK) 的表达.
主要成果:
- 在HK-2细胞中,PFOS暴露显著增加了KIM-1表达和ERS标记物 (GRP78,ATF6,IRE1,PERK).
- PFOS提高了MDA和细胞内铁水平,同时降低了GSH和GPX-4水平.
- 用fer-1治疗作为ferroptosis的对照.
结论:
- 通过铁亡和内质网膜应激,PFOS会损害HK-2细胞.
- 这些发现为了解PFOS对脏的毒性提供了理论基础.
- 这项研究突出了涉及PFOS诱导毒性的特定分子途径.
更多相关视频
相关概念视频
01:16Necrosis
4.3K
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...
4.3K
01:37The Unfolded Protein Response
4.4K
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...
4.4K
01:32Export of Misfolded Proteins out of the ER
3.5K
After folding, the ER assesses the quality of secretory and membrane proteins. The correctly folded proteins are cleared by the calnexin cycle for transport to their final destination, while misfolded proteins are held back in the ER lumen. The ER chaperones attempt to unfold and refold the misfolded proteins but sometimes fail to achieve the correct native conformation. Such terminally misfolded proteins are then exported to the cytosol by ER-associated degradation or ERAD pathway for...
3.5K
01:31Regulation 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