氧酸通过抑制Sirtuin脱酶活动
Kelsey Bohl1, Sarah L Wynia-Smith1, Rachel A Jones Lipinski1
1Department of Biochemistry, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, United States.
Biochemistry
|September 10, 2024
概括
衰老氧化剂过氧酸盐通过修改它们来抑制Sirtuin酶,从而可能增加对与年龄有关的疾病的易感性. 这项研究研究过氧酸盐.
科学领域:
- 生物化学 生物化学
- 酶学 是一种酶学.
- 分子生物学分子生物学
背景情况:
- 赛尔图因是NAD+依赖的脱乙酶,对细胞保护至关重要.
- 失去了Sirtuin活动与衰老和疾病有关.
- 氧化 (NO) 衍生的修饰,如S-化抑制sirtuins.
研究的目的:
- 为了比较过氧酸盐 (ONOO−) 对人类素脱酶活性的影响.
- 为了识别sirtuins中过氧酸诱导的翻译后修饰.
主要方法:
- 用过氧酸盐供体 (SIN-1) 治疗人类素异型 (SIRT1-3,5,6).
- 对Sirtuin脱酶活性的测定.
- 质谱测量用于识别蛋白质的修饰 (氨酸化,氨酸硫化).
主要成果:
- 过氧酸盐抑制了SIRT1,SIRT2,SIRT3,SIRT5和SIRT6脱酶的活性.
- 抑制与多种sirtuin异形中提洛辛化增加相关.
- 在SIRT1,SIRT3,SIRT5和SIRT6的催化核内发现了新型的氨酸化位点.
- 只有在SIRT1中检测到过氧酸介导的氨酸硫化,在SIRT6中检测到暂时的硫化和二硫化键形成.
结论:
- 过氧酸盐是一种与衰老相关的氧化剂,在翻译后修改并抑制关键的人类酸酶.
- 催化核心内的罗斯化是抑制Sirtuin的可能机制.
- 这些发现表明,过氧酸盐诱导的锡图因抑制在与衰老相关的疾病易感性中起着作用.
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