ALDH2 Mediates 5-Nitrofuran Activity in Multiple Species

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

Research output: Contribution to journalArticlepeer-review

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 prodrugs 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 and zebrafish, as well as human in vitro systems, to assess the biological activity of 5-nitrofurans, and we 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 prodrug, is dependent on zebrafish Aldh2 and 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 5-nitrofuran 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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