由GRP-78/PERK/CHOP信号介导的ERS涉及化物诱导的氨核细胞亡
Li Jinyi1,2, Yang Keyu3, Dai Shanshan1,2
1Key laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University, Xi'an, 710004, People's Republic of China.
Biological trace element research
|July 6, 2023
概括
过度的化物摄入会导致牙化,通过通过内质网膜应激 (ERS) 诱导细胞亡. 用4-PBA抑制ESR显示了牙化的治疗潜力.
科学领域:
- 生物化学 生物化学
- 细胞生物学 细胞生物学
- 毒理学 毒理学 毒理学
背景情况:
- 牙化是过量摄入的不良影响,可能涉及乳腺细胞亡.
- 化物诱导的乳腺细胞亡背后的精确分子信号通路尚不清楚.
研究的目的:
- 用细胞模型研究牙化病原性.
- 探索内细胞网膜应激 (ERS) 和亡在化物毒性的作用.
- 为了确定牙化的潜在治疗点.
主要方法:
- 建立了一个化细胞模型,使用小鼠乳腺细胞衍生LS8细胞.
- 通过CCK-8测定和流式细胞计量评估细胞活力和细胞亡.
- 利用高吞吐量测序,传输电子显微镜,qPCR和西方抹杀来分析分子变化.
- 研究了4-phenylbutyrate (4-PBA) 对化物诱导的细胞损伤的影响.
主要成果:
- 化 (NaF) 暴露降低了LS8细胞活力,并诱导了亡和形态变化.
- RNA测序揭示了细胞内膜网膜中的蛋白质处理受损,表明了ERS诱导.
- 通过GRP-78/PERK/CHOP信号通路调解的过度NaF显著诱导了ERS和亡.
- 观察到质矩阵蛋白酶KLK4的下调,并通过4-PBA治疗挽救了这种情况.
结论:
- 过度的化物会通过内细胞网膜应激诱导乳腺细胞亡.
- GRP-78/PERK/CHOP通路与化物诱导的ERS和亡有关.
- 抑制ERS为牙科化提供了潜在的治疗策略,其中KLK4表达是相关的标记物.
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