Set7/9通过通过阻断Sirt5的方式增强谷氨酸代谢来加剧缺血性脑损伤
Jinghuan Wang1, Subei Tan1,2, Yuyu Zhang1
1Shanghai Key Labortary of Vascular Lesions Regulation and Remodeling, Shanghai Pudong Hospital, Pharmacophenomics Laboratory, Human Phenome Institute, Fudan University, Shanghai, 201203, China.
Cell death and differentiation
|February 16, 2024
概括
甲基转移酶Set7/9在缺血性中风期间升高,降低保护性Sirt5.5的调节. 阻断Set7/9通过恢复Sirt5表达和降低谷氨酸和氨水平来减少脑损伤.
科学领域:
- 神经科学是一个神经科学.
- 分子生物学分子生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 异常的甲基转移酶Set7/9表达与各种疾病有关.
- Set7/9在缺血性中风病原体中的作用尚不清楚.
- 众所周知,Sirt5是一种脱乙酶,可以防止受伤.
研究的目的:
- 调查Set7/9在缺血性中风中的作用.
- 阐明Set7/9影响Sirt5表达和神经元损伤的分子机制.
主要方法:
- 在小鼠模型中诱导缺血损伤.
- 对Set7/9和Sirt5表达水平的分析.
- 蛋白质组分析以确定相互作用的蛋白质.
- 染色体免疫沉以评估促进体结合.
- 评估氨和谷氨酸水平.
主要成果:
- 缺血性损伤迅速增加了Set7/9表达,并降低了Sirt5水平.
- Set7/9促进染色体同源1 (Cbx1) 与H3K9me2/3结合,在Sirt5促进体形成抑制体.
- 这种机制抑制了Sirt5转录,导致减少了谷氨酸胺酶的脱乙烯化,增加了兴奋毒性.
- 阻止Set7/9可以恢复Sirt5的表达,并改善缺血性脑损伤.
结论:
- Set7/9-Sirt5轴是缺血性中风损伤的关键调节器.
- 通过Set7/9介导的Sirt5抑制通过谷氨酸酶调节促进激发性毒性.
- 准Set7/9-Sirt5通路为缺血性中风提供了一个潜在的治疗策略.
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