抗癌植物二次代谢物从染色体中驱逐链接组合基因素H1.2 激活I型干扰素信号传递
Olga Vlasova1, Irina Antonova1, Khamis Magomedova1
1N. N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia, 24 Kashirskoe Shosse, 115522 Moscow, Russia.
International journal of molecular sciences
|January 11, 2025
概括
某些抗癌植物化合物可以通过去除链接基因素,激活I型干扰素信号传递和有时LINE1表达来破坏染色质的稳定性. 这揭示了一种新的机制,将染色质变化与免疫反应联系起来.
科学领域:
- 分子生物学分子生物学
- 免疫学 免疫学 免疫学
- 药理学 药理学是指药理学的学科.
背景情况:
- 此前曾研究过具有抗癌活性的DNA结合植物二次代谢物 (PSM).
- 在15种PSM中,有11种被发现会耗尽染色素结合的链接组合基因素H1.2和/或H1.4.
- 染色体重塑可以调节重复的元素,触发干扰素 (IFN) 反应.
研究的目的:
- 调查PSM对链接基因组位的影响及其对I型IFN信号传递和LINE1表达的影响.
- 为了确定抗癌PSM的链接组合素驱逐与IFN信号激活是否相关.
- 探索LINE1表达在这个过程中的作用.
主要方法:
- 用各种PSM对待HeLa细胞.
- 使用流细胞计的光记者测定用于测量IFN信号传输.
- 免疫光染色和定量RT-PCR评估了基质子的位置和LINE1表达.
主要成果:
- 八种PSM驱逐链接组合素H1.2显著激活了I型IFN信号;白醇,柏柏林,基因斯坦,海豚胺,纳灵宁和黄素也诱导了LINE1的表达.
- 菲塞丁和奎尔丁诱导了H1.2驱逐和IFN信号,但没有LINE1表达.
- 消耗H1.4的PSM (黄素,血红素,甲醇) 显示 IFN激活的强度较小,没有LINE1变化.
- 四种不引起组素驱逐的PSM没有显示IFN信号或LINE1激活.
结论:
- 抗癌DNA结合的PSM可以通过耗尽链接组合基因素H1.2.2.来破坏染色质的稳定性.
- 这种染色体不稳定与增强的I型IFN信号传输有关.
- LINE1表达经常伴随并可能影响这种IFN激活,揭示了一个新的机制.
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