Radjendirane V, Joseph P, Lee Y H, Kimura S, Klein-Szanto A J, Gonzalez F J, Jaiswal A K
Department of Pharmacology, Baylor College of Medicine, Houston, Texas 77030-3498, USA.
J Biol Chem. 1998 Mar 27;273(13):7382-9. doi: 10.1074/jbc.273.13.7382.
NAD(P)H:quinone oxidoreductase 1 (NQO1) is a flavoenzyme that catalyzes two-electron reductive metabolism and detoxification of quinones and their derivatives leading to protection of cells against redox cycling and oxidative stress. To examine the in vivo role of NQO1, a NQO1-null mouse was produced using targeted gene disruption. Mice lacking NQO1 gene expression showed no detectable phenotype and were indistinguishable from wild-type mice. However, NQO1-null mice exhibited increased toxicity when administered menadione compared with wild-type mice. These results establish a role for NQO1 in protection against quinone toxicity. The NQO1-null mice are a model for NQO1 deficiency in humans and can be used to determine the role of this enzyme in sensitivity to toxicity and carcinogenesis.
烟酰胺腺嘌呤二核苷酸磷酸（NAD(P)H）：醌氧化还原酶1（NQO1）是一种黄素酶，催化醌及其衍生物的双电子还原代谢和解毒，从而保护细胞免受氧化还原循环和氧化应激的影响。为了研究NQO1在体内的作用，利用靶向基因敲除技术培育出了NQO1基因缺失小鼠。缺乏NQO1基因表达的小鼠未表现出可检测到的表型，与野生型小鼠没有区别。然而，与野生型小鼠相比，给予甲萘醌时，NQO1基因缺失小鼠表现出更高的毒性。这些结果确立了NQO1在预防醌毒性方面的作用。NQO1基因缺失小鼠是人类NQO1缺乏症的模型，可用于确定该酶在毒性敏感性和致癌作用中的作用。
