An approach to evaluate two-electron reduction of 9,10-phenanthraquinone and redox activity of the hydroquinone associated with oxidative stress
An approach to evaluate two-electron reduction of 9,10-phenanthraquinone and redox activity of the hydroquinone associated with oxidative stress
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DOI：
10.1016/j.freeradbiomed.2007.05.021
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发表时间：
2007-09-01
影响因子：
7.4
通讯作者：
Kumagai, Yoshito
中科院分区：
文献类型：
--
作者：
Taguchi, Keiko;Fujii, Sayako;Kumagai, Yoshito
醌类化合物广泛用作药物或氧化还原剂。化学性质是基于对电子供体的反应。9，10-菲蒽醌（PQ），这是一种在空气中的颗粒物污染的醌，强氧化还原循环，而不是迈克尔加成，与电子供体。PQ的氧化还原循环导致其毒性，随后产生活性氧（ROS）。醌类的脱乙酰基反应通常被认为是双电子还原形成对苯二酚。然而，PQ的对苯二酚9，10-二羟基菲（PQH（2））本身从未被检测到，因为它非常不稳定。本文成功地检测了PQH（2）的稳定衍生物9，10-二乙酰氧基菲（DAP）。然而，较高浓度的PQ（> 4 μ M）与PQH（2）不成比例地形成，产生9，10-菲蒽醌自由基（PQ（中心点-）），它是PQ的单电子还原产物。在使用DAP作为PQH（2）的前体的细胞实验中，显示PQH（2）在PQ的氧化蛋白质损伤和细胞毒性中起关键作用，显示PQ的双电子还原也可以引发氧化还原循环，从而引起氧化应激依赖性细胞毒性。(c)2007年爱思唯尔公司All rights reserved.
Quinones are widely used as medicines or redox agents. The chemical properties are based on the reactions against an electron donor. 9, 10-Phenanthraquinone (PQ), which is a quinone contaminated in airborne particulate matters, fortes redox cycling, not Michael addition, with electron donors. Redox cycling of PQ contributes to its toxicity, following generation of reactive oxygen species (ROS). Detoxification of quinones is generally thought to be two-electron reduction forming hydroquinones. However, a hydroquinone of PQ, 9,10-dihydroxyphenanthrene (PQH(2)), has been never detected itself, because it is quite unstable. In this paper, we succeeded in detecting PQH(2) as its stable derivative, 9,10-diacetoxyphenanthrene (DAP). However, higher concentrations of PQ (> 4 mu M) form disproportionately with PQH(2), producing the 9,10-phenanthraquinone radical (PQ(center dot-)) which is a one-electron reducing product of PQ. In cellular experiments using DAP as a precursor of PQH(2), it was shown that PQH(2) plays a critical role in the oxidative protein damage and cellular toxicity of PQ, showing that two-electron reduction of PQ can also initiate redox cycling to cause oxidative stress-dependent cytotoxicity. (c) 2007 Elsevier Inc. All rights reserved.