ALDH2 mediates 5-nitrofuran activity in multiple species

Linna Zhou, Hironori Ishizaki, Michaela Spitzer, Kerrie Taylor, Nicholas Temperley, Stephen Johnson, Paul Brear, Philippe Gautier, Zhiqiang Zeng, Amy Mitchell, Vikram Narayan, Ewan McNeil, David Melton, Terry K Smith, Mike Tyers, Nicholas James Westwood, Elizabeth Patton

Research output: Contribution to journalArticlepeer-review

41 Citations (Scopus)
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Abstract

Understanding how drugs work in vivo is critical for drug design and for maximizing the potential of currently available drugs. 5-nitrofurans are a class of pro-drugs widely used to treat bacterial and trypanosome infections, but despite relative specificity 5-nitrofurans often cause serious toxic side-effects in people. Here, we use yeast, zebrafish and human in vitro systems to assess the biological activity of 5-nitrofurans, and identify a conserved interaction between aldehyde dehydrogenase (ALDH) 2 and 5-nitrofurans across these species. In addition, we show that the activity of nifurtimox, a 5-nitrofuran anti-trypanosome pro-drug, is dependent on zebrafish Aldh2 and that nifurtimox is a substrate for human ALDH2. This study reveals a conserved and biologically relevant ALDH2-5-nitrofuran interaction that may have important implications for managing the toxicity of 5nitrofuran treatment.
Original languageEnglish
Pages (from-to)883-892
Number of pages10
JournalChemistry and Biology
Volume19
Issue number7
DOIs
Publication statusPublished - 27 Jul 2012

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