Shimada Hideaki, Hirashima Takaomi, Imamura Yorishige
Faculty of Education, Kumamoto University, 2-40-1, Kurokami, Kumamoto 860-8555, Japan.
Eur J Pharmacol. 2006 Jul 1;540(1-3):46-52. doi: 10.1016/j.ejphar.2006.04.050. Epub 2006 May 7.
We have recently purified a tetrameric carbonyl reductase from the cytosolic fraction of pig heart (pig heart carbonyl reductase). Since pig heart carbonyl reductase efficiently reduces all-trans retinal as the endogenous substrate, it probably plays an important role in retinoid metabolism in the heart. The purpose of the present study was to evaluate the inhibitory effects of quinones and flavonoids on the reduction of all-trans retinal to all-trans retinol catalyzed by pig heart carbonyl reductase, using pig heart cytosol. Of quinones tested, 9,10-phenanthrenequinone, a component of diesel exhaust particles, was the most potent inhibitor for the all-trans retinal reduction, and a significant inhibition was also observed for plumbagin and menadione. The order of the inhibitory potencies for flavonoids was kaempferol > quercetin > genistein > myricetin = apigenin = daidzein. However, the inhibitory potencies of flavonoids were much lower than that of 9,10-phenanthrenequinone. 9,10-Phenanthrenequinone competitively inhibited the all-trans retinal reduction, whereas kaempferol exhibited a mixed-type inhibition. It is likely that 9,10-phenanthrenequinone strongly inhibits the reduction of all-trans retinal to all-trans retinol by acting as the substrate inhibitor of pig heart carbonyl reductase present in pig heart cytosol.
我们最近从猪心脏的胞质部分纯化出一种四聚体羰基还原酶（猪心脏羰基还原酶）。由于猪心脏羰基还原酶能有效地将全反式视黄醛作为内源性底物进行还原，它可能在心脏的类维生素A代谢中发挥重要作用。本研究的目的是利用猪心脏胞质溶胶评估醌类和黄酮类化合物对猪心脏羰基还原酶催化全反式视黄醛还原为全反式视黄醇的抑制作用。在所测试的醌类中，柴油废气颗粒的成分之一9,10 - 菲醌是全反式视黄醛还原的最有效抑制剂，对于白花丹醌和甲萘醌也观察到显著抑制作用。黄酮类化合物的抑制效力顺序为山奈酚＞槲皮素＞染料木黄酮＞杨梅素 = 芹菜素 = 大豆苷元。然而，黄酮类化合物的抑制效力远低于9,10 - 菲醌。9,10 - 菲醌竞争性抑制全反式视黄醛还原，而山奈酚表现出混合型抑制。9,10 - 菲醌很可能通过作为猪心脏胞质溶胶中存在的猪心脏羰基还原酶的底物抑制剂，强烈抑制全反式视黄醛向全反式视黄醇的还原。
