TY - JOUR
T1 - ALDH2 mediates 5-nitrofuran activity in multiple species
AU - Zhou, Linna
AU - Ishizaki, Hironori
AU - Spitzer, Michaela
AU - Taylor, Kerrie
AU - Temperley, Nicholas
AU - Johnson, Stephen
AU - Brear, Paul
AU - Gautier, Philippe
AU - Zeng, Zhiqiang
AU - Mitchell, Amy
AU - Narayan, Vikram
AU - McNeil, Ewan
AU - Melton, David
AU - Smith, Terry K
AU - Tyers, Mike
AU - Westwood, Nicholas James
AU - Patton, Elizabeth
PY - 2012/7/27
Y1 - 2012/7/27
N2 - 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.
AB - 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.
U2 - 10.1016/j.chembiol.2012.05.017
DO - 10.1016/j.chembiol.2012.05.017
M3 - Article
C2 - 22840776
SN - 1074-5521
VL - 19
SP - 883
EP - 892
JO - Chemistry and Biology
JF - Chemistry and Biology
IS - 7
ER -