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5hmC的修改调节R循环积累,以应对应力
Xingyun Xu1,2, Junjie Wang2, Wenjuan Wang2
1Department of Neurology, The First Affiliated Hospital of Soochow University, Soochow University, Suzhou, China.
Frontiers in psychiatry
|June 26, 2023
概括
慢性压力会增加R循环,DNA损伤和基因组不稳定性. 通过NONO-Tet复合体,DNA5基甲基细胞素 (5hmC) 修改会负面调节R循环,为抑郁症提供潜在的治疗点.
科学领域:
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 神经科学是一个神经科学.
- 基因组学就是基因组学.
背景情况:
- R环,RNA-DNA混合体,是转录的副产品,与DNA损伤和基因组不稳定性有关.
- 十-十一转位 (Tet) 蛋白质通过氧化5-甲基细胞因子到5-基甲基细胞因子 (5hmC) 来修改DNA.
- R环和5hmC修饰之间的确切关系在很大程度上仍未定义.
研究的目的:
- 研究DNA 5hmC修饰在应力下R循环积累中的调节作用.
- 阐明分子机制,包括蛋白质相互作用,是R循环调节的基础.
- 确定压力诱导的神经疾病的潜在治疗点.
主要方法:
- 在慢性束压力下,对小鼠前额叶皮质 (PFC) 中R-循环和5hmC水平的分析.
- 使用维生素C和化合物SC-1进行5hmC水平的药理操作.
- 研究Tet和NONO蛋白相互作用及其在R循环形成中的作用,使用免疫沉和基因沉默.
- 在压力小鼠中评估DNA损伤和fluoxetine的治疗疗效.
主要成果:
- 慢性压力增加了R循环积累,并降低了PFC中的5hmC水平.
- 提高5hmC减少了R循环,而降低5hmC增加了R循环,证实了反向关系.
- 蛋白和NONO形成一个复合物,抑制R循环的形成;任何蛋白质的缺乏都会增加R循环.
- 在受压力的小鼠中,NONO蛋白水平下降; 素治疗恢复了NONO,减少了R循环,并减轻了DNA损伤.
结论:
- 在压力下,DNA 5hmC 修改通过NONO-Tet 复合体负面调节R循环积累.
- 压力会降低NONO蛋白水平,导致R循环积累.
- 针对NONO-Tet复合体和5hmC修饰,为抑郁症提供了一个有希望的治疗策略.
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