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

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    25 Citations (Scopus)

    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 & Biology
    Volume19
    Issue number7
    DOIs
    Publication statusPublished - 27 Jul 2012

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    Zhou, L., Ishizaki, H., Spitzer, M., Taylor, K. L., Temperley, N. D., Johnson, S. L., Brear, P., Gautier, P., Zeng, Z., Mitchell, A., Narayan, V., McNeil, E. M., Melton, D. W., Smith, T. K., Tyers, M., Westwood, N. J., & Patton, E. E. (2012). ALDH2 mediates 5-nitrofuran activity in multiple species. Chemistry & Biology, 19(7), 883-892. https://doi.org/10.1016/j.chembiol.2012.05.017