重复暴露于激素诱导了通过破坏p53依赖的线粒体功能的表皮细胞-介质细胞过渡式转变
Shan Shan1, Xiaoyu Chen1, Aiqing Wang2
1School of Public Health, Suzhou Medical College of Soochow University, 199 Renai Road, Suzhou, Jiangsu 215123, China.
Toxicology research
|December 25, 2023
概括
暴露会通过破坏线粒体功能和促进细胞变化引起肺癌. p53基因及其通路可能会防止引发的肺损伤.
科学领域:
- 环境健康 环境健康
- 分子生物学分子生物学
- 癌症研究 癌症研究
背景情况:
- 是肺癌的重要危险因素之一.
- 瘤抑制基因p53对于线粒体功能至关重要.
- 了解p53在激素诱导的致癌过程中的作用至关重要.
研究的目的:
- 调查p53和p53-响应途径在诱导的致癌过程中的关联.
- 评估暴露对细胞和线粒体功能的影响.
- 确定p53对引起的肺损伤的保护作用.
主要方法:
- 在暴露于子后,评估恶性特征,细胞周期,细胞亡,ATP,ROS和BEAS-2B细胞和小鼠肺组织中的mtDNA拷贝数.
- 分析了线粒体能量代谢的生物标志物,包括TIGAR,p53R2和SCO2蛋白表达.
- 研究了p53缺乏对引发的细胞和线粒体变化的影响.
主要成果:
- 在BEAS-2B细胞中,暴露诱导了类似于上皮层-介质酶过渡 (EMT) 的变化,增加了增殖和迁移.
- 观察到线粒体功能障碍,包括ATP减少,ROS增加,mtDNA复制数增加,细胞亡和G2/M细胞周期停止.
- 暴露将能量代谢从有氧呼吸转移到糖溶解,并改变了蛋白质表达 (TIGAR,p53R2,SCO2,p53).
结论:
- 暴露会通过线粒体功能障碍诱导类似EMT的转变.
- 激活p53和相关途径可能会提供对诱导的肺损伤的保护.
- 缺少p53会加剧线粒体功能障碍和恶性状的特征.
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