ALDH2 mediates 5-nitrofuran activity in multiple species
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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.
Zhou , L , Ishizaki , H , Spitzer , M , Taylor , K , Temperley , N , Johnson , S , Brear , P , Gautier , P , Zeng , Z , Mitchell , A , Narayan , V , McNeil , E , Melton , D , Smith , T K , Tyers , M , Westwood , N J & Patton , E 2012 , ' ALDH2 mediates 5-nitrofuran activity in multiple species ' , Chemistry and Biology , vol. 19 , no. 7 , pp. 883-892 . https://doi.org/10.1016/j.chembiol.2012.05.017
Chemistry and Biology
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