title: NQO2 is a reactive oxygen species generating off-target for acetaminophen.
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.
authors.affiliation: Division of Cell and Developmental Biology, College of Life Sciences, University of Dundee , DD1 5EH Dundee, Scotland , U.K.
authors.forename: Teemu P
authors.initials: TP
authors.lastname: Miettinen
authors.forename: Mikael
authors.initials: M
authors.lastname: Björklund
mesh_terms: D000082:Acetaminophen / Q000009:adverse effects / Q000737:chemistry* / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D066298:In Vitro Techniques; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D011808:Quinone Reductases / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D017382:Reactive Oxygen Species; D000082:Acetaminophen; C419642:NRH - quinone oxidoreductase2; D011808:Quinone Reductases
keywords: CETSA; NQO2; acetaminophen; drug target; paracetamol; quinone reductase 2; superoxide