Redox reactions of the FAD-containing apoptosis-inducing factor (AIF) with quinoidal xenobiotics: a mechanistic study.
Redox reactions of the FAD-containing apoptosis-inducing factor (AIF) with quinoidal xenobiotics: a mechanistic study.
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DOI：
10.1016/j.abb.2011.05.015
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发表时间：
2011-08-15
影响因子：
3.9
通讯作者：
Cenas, Narimantas
中科院分区：
文献类型：
--
作者：
Miseviciene, Lina;Anusevicius, Zilvinas;Sarlauskas, Jonas;Sevrioukova, Irina F.;Cenas, Narimantas
线粒体凋亡诱导因子（AIF）是一种含有FAD的蛋白质，在一定条件下易位到细胞核并引起程序性细胞死亡，即凋亡。AIF的致突变作用是氧化还原控制的，因为NADH还原的AIF二聚体对DNA的亲和力低于氧化单体。为了进一步了解AIF的机制，我们研究了它与一系列醌氧化剂的相互作用，包括一些抗癌醌。我们的数据表明，由AIF催化的NADH：醌氧化还原遵循“乒乓”方案，还原半反应是限速的和FADH-NAD+电荷转移复合物作为电子供体。AIF对苯并和萘醌具有相同的反应性，但可以区分具有较高芳香环数的结构。醌的反应性主要由它们的单电子还原电位来定义，而取代基的大小和性质起次要作用。AIF不太可能显著促进低潜力醌式抗癌醌的生物还原活化。然而，当存在显着过量的NADH时，高电位醌类（例如有毒的天然化合物萘茜）会使AIF保持氧化状态。因此，这些化合物可以防止AIF的还原形式在体内的积累，并增强AIF介导的细胞凋亡。
Mitochondrial apoptosis-inducing factor (AIF) is a FAD-containing protein that under certain conditions translocates to the nucleus and causes a programmed cell death, apoptosis. The apoptogenic action of AIF is redox controlled as the NADH-reduced AIF dimer has lower affinity for DNA than the oxidized monomer. To gain further insights into the mechanism of AIF, we investigated its interaction with a series of quinone oxidants, including a number of anticancer quinones. Our data indicate that the NADH:quinone oxidoreduction catalyzed by AIF follows a “ping-pong” scheme, with the reductive half-reaction being rate-limiting and the FADH--NAD+ charge-transfer complex serving as an electron donor. AIF is equally reactive toward benzo- and naphthoquinones, but may discriminate structures with a higher number of aromatic rings. The reactivity of quinones is mainly defined by their one-electron reduction potential, whereas the size and nature of the substituents play a minor role. AIF is unlikely to significantly contribute to bioreductive activation of low-potential quinoidal anticancer quinones. However, high-potential quinones, e.g. a toxic natural compound naphthazarin, maintain AIF in the oxidized state when a significant excess of NADH is present. Thus, these compounds may prevent the accumulation of the reduced form of AIF in vivo, and enhance AIF-mediated apoptosis.
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氧化还原诱导因子中的氧化还原连接构象动力学。
影响因子：
5.6
作者：
Sevrioukova, Irina F.
通讯作者：
Sevrioukova, Irina F.
DOI：
10.1016/0005-2728(70)90220-3
发表时间：
1970-01-01
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
IYANAGI, T;YAMAZAKI, I
通讯作者：
YAMAZAKI, I
影响因子：
4.6
作者：
Srinivas, P;Gopinath, G;Srinivas, G
通讯作者：
Srinivas, G
影响因子：
8
作者：
Candé, C;Vahsen, N;Kroemer, G
通讯作者：
Kroemer, G
影响因子：
3.6
作者：
MCCLURE, JD
通讯作者：
MCCLURE, JD