ресвератрол可以保护HepG2细胞免受脱氧尼瓦诺诱导的铁亡
Pengju Wang1, Qing Yao1, Dan Zhu1
1Medicine Research Institute, Xianning Medical College, Hubei University of Science and Technology, Xianning 437100, PR China.
Toxicology
|July 7, 2023
概括
脱氧尼瓦伦醇 (DON) 通过铁亡导致肝细胞死亡. 复星 (Res) 通过通过SLC7A11-GSH-GPX4通路抑制铁化,从而防止DON的毒性.
科学领域:
- 毒理学 毒理学 毒理学
- 细胞生物学 细胞生物学
- 生物化学 生物化学
背景情况:
- 脱氧尼瓦伦醇 (DON) 是一种普遍存在的真菌毒素,导致肝细胞死亡.
- DON诱导的肝毒性机制,特别是新的细胞死亡途径,需要进一步阐明.
- 铁,一种独特的依赖铁的细胞死亡形式,与各种毒性有关.
研究的目的:
- 为了研究铁化在脱氧尼瓦伦醇 (DON) 诱导的HepG2细胞毒性的作用.
- 探索白醇 (Res) 对DON诱导的铁亡的保护作用.
- 阐明了Res对DON毒性的抗性作用背后的分子机制.
主要方法:
- 用DON和/或Res对待HepG2细胞.
- 评估了细胞活力,增殖,与铁死相关的基因表达 (GPX4,SLC7A11,Nrf2),脂质过氧化 (MDA,4-HNE),活性氧物种 (ROS) 和Fe (II) 水平.
主要成果:
- DON暴露导致GPX4,SLC7A11和Nrf2的表达减少,Fe (II) 过载增加,脂质过氧化和ROS产生,诱导铁亡.
- 复星预治疗逆转了DON诱导的变化,减弱了铁亡,并改善了细胞活力和增殖.
- 复星通过激活SLC7A11-GSH-GPX4信号通路来表现出抗费洛的作用.
结论:
- 复星可以改善HepG2细胞中Deoxynivalenol诱导的铁亡.
- 这项研究确定了铁亡作为DON肝毒性的关键机制.
- Resveratrol显示出作为治疗剂对抗DON诱导的肝损伤的潜力.
相关概念视频
Necrosis
4.6K
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...
4.6K
The Unfolded Protein Response
4.8K
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...
4.8K
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


