死亡亡需要SIRT2吗?
Kim Newton1, Joanne M Hildebrand2, Zhirong Shen3
1Genentech, Inc., South San Francisco, California 94080, USA.
Nature
|February 28, 2014
概括
这项研究研究了SIRT2在亡中的作用,这是一种编程细胞死亡的形式. 研究人员发现,抑制或去除SIRT2并不能保护细胞免受亡,质疑其在这种途径中的重要性.
科学领域:
- 细胞生物学 细胞生物学
- 细胞死亡的分子机制
背景情况:
- 一类蛋白质的Sirtuins通过脱乙烯化来调节细胞过程.
- 以前的研究表明,SIRT2对于亡,即受调节的细胞死亡途径至关重要.
研究的目的:
- 确认和调查SIRT2在亡中的作用.
- 挑战SIRT2对死的要求现有的假设.
主要方法:
- 使用多种SIRT2抑制剂 (AGK2) 和基因沉默技术 (siRNAs).
- 采用了淘汰赛小鼠模型 (Sirt2-/-) 和野生类型的对照.
- 评估了对瘤死亡因子 (TNF) 和系统性炎症反应综合征 (SIRS) 诱导的细胞死亡反应.
主要成果:
- 抑制或消耗SIRT2并没有提供对死的保护.
- 与野生类型小鼠相比,Sirt2-/-小鼠对TNF诱导的SIRS的敏感性增加.
- 缺乏Ripk3 (Ripk3-/-) 的小鼠对亡有抗性,作为阳性对照.
结论:
- 这些发现挑战了SIRT2在亡途径中的既定作用.
- 如前所述,SIRT2可能不是亡的关键调节者.
- 需要进一步的研究,以充分阐明SIRT2在细胞死亡中的作用.
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