透露双A和双S通过不同的蛋白质标诱导铁亡
Yanwei Wang1,2, Jiahui Zhao1,3, Yong Chen1
1College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
Environmental science & technology
|October 10, 2025
概括
长期暴露在双A (BPA) 和双S (BPS) 中会通过铁死破坏肝功能. 乙A针对谷氨过氧化酶4 (GPX4),而乙S则影响酸盐激酶M2 (PKM2),揭示了肝细胞损伤的独特分子机制.
科学领域:
- 毒理学 毒理学 毒理学
- 细胞生物学 细胞生物学
- 生物化学 生物化学
背景情况:
- 长期暴露于双醇会破坏肝功能.
- 铁亡也涉及,但机制尚不清楚.
研究的目的:
- 在肝细胞中阐明由双A (BPA) 和双S (BPS) 诱导的铁亡的机制.
- 确定涉及双诱导肝损伤的分子标和途径.
主要方法:
- 整合性化学蛋白质组学和非目标代谢组学.
- 细胞热转移试验 (CETSA),表面等离子体共振 (SPR) 和分子对接.
- 用目标过度表达的功能救援实验.
主要成果:
- 通过抑制GPX4.4,BPA诱导了一个明显的铁性表现型.
- 通过抑制PKM2,BPS通过抑制PKM2引起了中度的铁类表型,导致谷氨酸耗尽.
- 过度表达GPX4可以逆转BPA诱导的铁;过度表达PKM2可以缓解BPS诱导的细胞毒性.
结论:
- 双醇诱导的铁化通过不同的分子点 (BPA的GPX4,BPS的PKM2) 发生.
- 了解目标异质性提供了对双毒性的机械洞察力.
- 这些发现可能会为未来对双醇的安全性评估提供信息.
更多相关视频
07:08Long-term Behavioral and Reproductive Consequences of Embryonic Exposure to Low-dose Toxicants
Published on: March 6, 2018
6.5K
08:28Assessment of the Effects of Endocrine Disrupting Compounds on the Development of Vertebrate Neural Network Function Using Multi-electrode Arrays
Published on: April 26, 2018
6.4K
相关概念视频
Necrosis
6.3K
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...
6.3K
Covalently Linked Protein Regulators
8.7K
Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein....
These groups modify specific amino acids in a protein....
8.7K
Regulation of Angiogenesis and Blood Supply
3.3K
Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits. Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
3.3K
