TRPML1 通过通过伴侣介导的自产生铁,从而促进诱导的毒性
Lei Liu1, Chao Luo2, Dongnan Zheng2
1Department of Pathology, Affiliated Hospital of Nantong University, Nantong, 226001, China; Department of Occupational Medicine and Environmental Toxicology, Nantong Key Laboratory of Environmental Toxicology, School of Public Health, Nantong University, Nantong, 226019, China.
概括
(Sb) 通过诱导管状上皮细胞 (RTEC) 的铁亡,导致损伤. 恢复TRPML1水平可以防止Sb诱导的毒性和铁.
科学领域:
- 毒理学 毒理学 毒理学
- 细胞生物学 细胞生物学
- 脏生理学 脏生理学
背景情况:
- 铁亡与损伤有关.
- (Sb) 诱导的毒性机制,特别是与铁亡的联系,仍然不清楚.
研究的目的:
- 调查铁化在Sb诱导的毒性中的作用和机制.
- 探索TRPML1作为Sb诱导损伤的治疗标的潜力.
主要方法:
- 利用管状上皮细胞 (RTEC) 来研究Sb暴露.
- 评估了铁灭菌标记物,活性氧物种 (ROS) 水平和伴侣介导自 (CMA) 途径蛋白.
- 研究了TRPML1调节和N-乙半氨酸 (NAC) 治疗的影响.
主要成果:
- Sb诱导RTECs损伤和铁亡,通过抑制铁亡或消除ROS而得到改善.
- 暴露于Sb激活了CMA,导致GPX4的溶酶体降解和随后的铁亡.
- 通过调节CMA相关蛋白质,TRPML1的升调减轻了Sb诱导的RTEC损伤和铁亡.
结论:
- 由Sb诱导的毒性包括由CMA依赖的GPX4.4降解介导的铁亡.
- 由ROS加剧的TRPML1缺陷推动了这一过程.
- TRPML1是Sb诱导的损伤的潜在治疗标.
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