一个单个蛋白质的substoichiometric hydroxynonenylation 重复整细胞刺激的抗氧化反应
Saba Parvez1, Yuan Fu, Jiayang Li
1Department of Chemistry and Chemical Biology, Cornell University , Ithaca, New York 14853, United States.
Journal of the American Chemical Society
|December 30, 2014
概括
用脂质衍生电友 (LDEs) 修改单个蛋白质,如4-hydroxynonenal (HNE),可以触发显著的细胞反应. 这项研究表明,即使在一个目标上进行轻微的HNEylation,也会激活抗氧化反应元素 (ARE).
科学领域:
- 蜂信号传输是如何进行的
- 生物化学 生物化学
- 分子生物学分子生物学
背景情况:
- 脂质衍生电友 (LDEs) 是修改蛋白质的关键小分子,影响细胞决策.
- 鉴定LDE对单个蛋白标的功能影响是具有挑战性的,因为它们具有广泛的反应性 (>700个由4-hydroxynonenal (HNE) 修饰的囊蛋白).
- 单个LDE修改激活下游氧化还原信号通路的能力在很大程度上仍未被探索.
研究的目的:
- 调查LDE对单个蛋白质点的修改是否足以触发特定的细胞反应.
- 为了确定是否针对单个蛋白质可以激活抗氧化剂反应元素 (ARE).
主要方法:
- 利用T-REX (可定位的反应电友和氧化剂) 技术,精确的时间和选择性修改细胞内的单一氧化还原开关.
- 在特定的蛋白质点上量化了HNEylation的水平.
- 测量了抗氧化剂反应元素 (ARE) 的激活强度.
主要成果:
- 在单个蛋白质点上,适度的HNEylation水平 (∼34%) 足以激活ARE.
- 来自单个目标修饰的ARE诱导的强度与从全球电友应力中观察到的强度相当.
- 这为哺乳动物细胞中单个点LDE修饰的生理意义提供了第一个证据.
结论:
- 通过LDEs单个目标的修改可以有效地引起显著的细胞反应,如ARE激活.
- 这一发现挑战了LDE介导信号传输需要广泛修改的概念.
- 这些结果强调了个体蛋白质修饰在哺乳动物生理学和氧化还原信号传递中的重要性.
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