Taguchi Keiko, Fujii Sayako, Yamano Shigeru, Cho Arthur K, Kamisuki Shinji, Nakai Yumi, Sugawara Fumio, Froines John R, Kumagai Yoshito
Doctoral Programs in Medical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan.
Free Radic Biol Med. 2007 Sep 1;43(5):789-99. doi: 10.1016/j.freeradbiomed.2007.05.021. Epub 2007 May 24.
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, forms 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 microM) form disproportionately with PQH(2), producing the 9,10-phenanthraquinone radical (PQ(-)) 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.
醌类化合物被广泛用作药物或氧化还原剂。其化学性质基于与电子供体的反应。9,10-菲醌（PQ）是一种存在于空气中颗粒物中的醌类污染物，它与电子供体形成氧化还原循环，而非迈克尔加成反应。PQ的氧化还原循环会在活性氧（ROS）生成后导致其毒性。醌类化合物的解毒通常被认为是通过两电子还原形成氢醌。然而，PQ的氢醌，即9,10-二羟基菲（PQH₂），从未被检测到，因为它非常不稳定。在本文中，我们成功地检测到了作为其稳定衍生物的9,10-二乙酰氧基菲（DAP）形式的PQH₂。然而，较高浓度的PQ（>4 microM）与PQH₂不成比例地形成，产生9,10-菲醌自由基（PQ⁻），它是PQ的单电子还原产物。在使用DAP作为PQH₂前体的细胞实验中，结果表明PQH₂在PQ的氧化蛋白质损伤和细胞毒性中起关键作用，这表明PQ的两电子还原也可引发氧化还原循环，从而导致氧化应激依赖性细胞毒性。
