Diphenyl diselenide [(PhSe) 2] inhibits Drosophila melanogaster δ-aminolevulinate dehydratase (δ-ALA-D) gene transcription and enzyme activity

Abstract

The main objective of the present study was to compare the inhibitory effect of diphenyl diselenide (PhSe) 2 and Pb 2+ on mice and fruit fly δ-Aminolevulinate dehydratase (δ-ALA-D). Optimum pH was quite different for mice (pH 6.5) and flies (pH 8.5). At pH 8.5, the inhibitory potency of (PhSe) 2 was higher for the fruit flies (IC 50 8.2 μmol/l) than for mice (IC 50 19.5 μmol/l). Pb 2+ inhibited mice δ-ALA-D at pH 6.5 (IC 50 6.2 μmol/l) and 8.5 (IC 50 5.6 μmol/l) with higher potency than the fly enzyme (IC 50 43.7 μmol/l). δ-ALA-D transcription was reduced by 15% in flies exposed to 0.3 mmol/kg (PhSe) 2, which is similar to the reduction observed in activity measured in the presence of dithiothreitol. The three-dimensional prediction by SWISS-PROT mouse and fly δ-ALA-D revealed differences in the number of hydrogen bonds and turns for the 2 enzymes. Sulfhydryl groups (−SH) that could be oxidized by (PhSe) 2 are conserved in the two sources of enzyme. Distinct responsiveness to pH, (PhSe) 2 and Pb 2+ of these enzymes may be related to subtle differences in tertiary or quaternary structure of mouse and fly δ-ALA-D. Furthermore, mechanism underlying enzyme inhibition after in vivo exposure seems to be different for Drosophila melanogaster and rodent enzymes.