NQO2是对乙酰氨基酚产生活性氧的脱靶效应。
NQO2 is a reactive oxygen species generating off-target for acetaminophen.
作者信息
Miettinen Teemu P, Björklund Mikael
机构信息
Division of Cell and Developmental Biology, College of Life Sciences, University of Dundee , DD1 5EH Dundee, Scotland , U.K.
出版信息
Mol Pharm. 2014 Dec 1;11(12):4395-404. doi: 10.1021/mp5004866. Epub 2014 Oct 24.
Abstract
The analgesic and antipyretic compound acetaminophen (paracetamol) is one of the most used drugs worldwide. Acetaminophen overdose is also the most common cause for acute liver toxicity. Here we show that acetaminophen and many structurally related compounds bind quinone reductase 2 (NQO2) in vitro and in live cells, establishing NQO2 as a novel off-target. NQO2 modulates the levels of acetaminophen derived reactive oxygen species, more specifically superoxide anions, in cultured cells. In humans, NQO2 is highly expressed in liver and kidney, the main sites of acetaminophen toxicity. We suggest that NQO2 mediated superoxide production may function as a novel mechanism augmenting acetaminophen toxicity.
摘要
止痛和解热化合物对乙酰氨基酚（扑热息痛）是全球使用最广泛的药物之一。对乙酰氨基酚过量也是急性肝毒性的最常见原因。在此我们表明，对乙酰氨基酚和许多结构相关化合物在体外和活细胞中与醌还原酶2（NQO2）结合，确立了NQO2作为一种新的脱靶靶点。NQO2调节培养细胞中对乙酰氨基酚衍生的活性氧水平，更具体地说是超氧阴离子水平。在人类中，NQO2在肝脏和肾脏中高表达，而肝脏和肾脏是对乙酰氨基酚毒性的主要部位。我们认为，NQO2介导的超氧产生可能作为增强对乙酰氨基酚毒性的一种新机制。
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