UBE2L3通过自性依赖性铁灭菌促进素诱导的血液毒性
Boshen Wang1, Fei Li2, Juan Hu1
1Jiangsu Provincial Center for Disease Prevention and Control, Nanjing, Jiangsu 210000, China; Key Laboratory of Environmental Medicine Engineering of Ministry of Education, School of Public Health, Southeast University, Nanjing, Jiangsu 210009, China.
Ecotoxicology and environmental safety
|July 26, 2024
概括
低剂量的暴露会损害造血功能. 研究人员确定了UBE2L3的降低调节,破坏了自细胞依赖的铁亡,并引起了血液毒性.
科学领域:
- 环境健康 环境健康
- 毒理学 毒理学 毒理学
- 分子生物学分子生物学
背景情况:
- 是普遍存在的环境污染物和健康危害.
- 低剂量暴露可能导致血液毒性,损害造血功能.
- 早期识别损害生物标志物对于风险评估至关重要.
研究的目的:
- 研究与低剂量暴露相关的早期造血损伤和生物标志物.
- 阐明素诱导的血毒性背后的分子机制.
主要方法:
- 前性队列研究和基因表达综合数据库分析.
- 液体染色学 双重质谱和共免疫沉.
- 通过过度表达/敲击实验,免疫光和电子显微镜进行蛋白质相互作用预测和验证的深度学习.
主要成果:
- 在暴露于的受试者中,检测到UBE2L3 (E2) 酶的显著下调.
- 发现UBE2L3与泛素蛋白联酶ZNF598 (E3) 相互作用,该联酶与自蛋白LAMP-2结合.
- UBE2L3通过ZNF598扰乱LAMP-2的泛化-降解,减少GPX4的表达,并激活自性依赖性铁,增加脂质过氧化.
结论:
- 在引发的血液毒性中,UBE2L3在早期的造血损伤中起作用.
- 该机制涉及调节自性依赖于铁灭的信号通路.
- 破坏UBE2L3导致铁亡的增加,并导致血液形成功能受损.
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