在环境相关的度下,6-PPD素对C. elegans的寿命造成损害:通过抑制线粒体UPR反应的机械洞察力
1Key Laboratory of Environmental Medicine Engineering of Ministry of Education, Medical School, Southeast University, Nanjing, China.
The Science of the total environment
|September 15, 2024
概括
在C. elegans中,6-PPD (6-PPDQ) 毒性与抑制的线粒体未折叠蛋白反应 (mt UPR) 有关. 基斯甲基化通路调节这种反应,影响在6-PPDQ暴露下寿命和线粒体功能.
科学领域:
- 环境毒理学环境毒理学
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
背景情况:
- 6-PPD (6-PPDQ) 是一种环境污染物,已知对水生生物有毒.
- 长期暴露于6-PPDQ会减少Caenorhabditis elegans的寿命,但潜在的分子机制,特别是线粒体调节,尚未完全理解.
研究的目的:
- 调查C. elegans中6-PPDQ毒性对寿命的分子基础,重点关注线粒体未折叠蛋白反应 (mt UPR).
- 探索质子甲基化在调节mt UPR和6-PPDQ毒性的作用.
主要方法:
- 利用C. elegans作为一个模型生物体.
- 使用HSP-6作为标记物评估mt UPR.
- 测量了atfs-1,ubl-5,dve-1,met-2,set-6,jmjd-1,2和jmjd-3.1.1的基因表达,这些基因表达的基因表达是不同的.
- 在神经元和肠道组织中使用RNA干扰 (RNAi).
- 评估了线粒体功能障碍和反应性氧物种 (ROS) 生产.
主要成果:
- 0.1和1μg/L的6-PPDQ激活了mt UPR并增加了atfs-1,ubl-5和dve-1的表达,而10μg/L抑制了mt UPR并降低了这些基因表达.
- 在神经元或肠道中hsp-6,atfs-1,ubl-5和dve-1的RNAi加剧了对长寿的6-PPDQ毒性.
- 6-PPDQ调节的基因组甲基转移酶 (met-2,set-6) 和脱甲基酶 (jmjd-1.2,jmjd-3.1) 的基因表达.
- 基因组修饰剂的RNAi在6-PPDQ暴露下改变了mt UPR基因表达和线虫的寿命.
- hsp-6RNAi增强了6-PPDQ诱导的线粒体功能障碍和ROS.
结论:
- 在C. elegans中,6-PPDQ诱导的长寿损伤与对mt UPR的抑制有关.
- 与素甲基化相关的信号在mt UPR和6-PPDQ毒性中起着调节作用.
- 这些发现阐明了涉及环境毒素反应的新型分子途径.
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