NQO2 is a reactive oxygen species generating off-target for acetaminophen

Teemu P. Miettinen; Mikael Björklund

doi:10.1021/mp5004866

NQO2 is a reactive oxygen species generating off-target for acetaminophen

Teemu P. Miettinen (Lead / Corresponding author), Mikael Björklund

Research output: Contribution to journal › Article › peer-review

73 Citations (Scopus)

236 Downloads (Pure)

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.

Original language	English
Pages (from-to)	4395-4404
Number of pages	10
Journal	Molecular Pharmaceutics
Volume	11
Issue number	12
Early online date	14 Oct 2014
DOIs	https://doi.org/10.1021/mp5004866
Publication status	Published - 1 Dec 2014

Keywords

acetaminophen
CETSA
drug target
NQO2
paracetamol
quinone reductase 2
superoxide

ASJC Scopus subject areas

Pharmaceutical Science
Molecular Medicine
Drug Discovery

Access to Document

10.1021/mp5004866

Publisher final version
ACS AuthorChoice - This is an open access article published under a Creative Commons Attribution (CC-BY)License, which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited.
Final published version, 3.23 MBLicence: CC BY

Cite this

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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.",

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AB - 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.

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KW - superoxide

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NQO2 is a reactive oxygen species generating off-target for acetaminophen

Abstract

Keywords

ASJC Scopus subject areas

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Aref#d: 22161. Regulation of Cell Size in Multicellular Organisms (Research Career Development Fellowship)

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NQO2 is a reactive oxygen species generating off-target for acetaminophen

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

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Aref#d: 22161. Regulation of Cell Size in Multicellular Organisms (Research Career Development Fellowship)

Cite this