Diphenyl diselenide [(PhSe)2] inhibits Drosophila melanogaster delta-aminolevulinate dehydratase (delta-ALA-D) gene transcription and enzyme activity.
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 delta-Aminolevulinate dehydratase (delta-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 micromol/l) than for mice (IC(50) 19.5 micromol/l). Pb(2+) inhibited mice delta-ALA-D at pH 6.5 (IC(50) 6.2 micromol/l) and 8.5 (IC(50) 5.6 micromol/l) with higher potency than the fly enzyme (IC(50) 43.7 micromol/l). delta-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 delta-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 delta-ALA-D. Furthermore, mechanism underlying enzyme inhibition after in vivo exposure seems to be different for Drosophila melanogaster and rodent enzymes.
Golombieski
R M
RM
Universidade Federal do Rio Grande do Sul, Departamento de Genética, Programa de Pós Graduação em Genética e Biologia Molecular, Porto Alegre, RS, Brazil. ronaldo@mail.ufsm.br
Graichen
D A S
DA
Pivetta
L A
LA
Nogueira
C W
CW
Loreto
E L S
EL
Rocha
J B T
JB
D000818:Animals; D001555:Benzene Derivatives / Q000633:toxicity*; D004331:Drosophila melanogaster / Q000201:enzymology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D008297:Male; D051379:Mice; D016566:Organoselenium Compounds / Q000633:toxicity*; D000623:Porphobilinogen Synthase / Q000037:antagonists & inhibitors / Q000235:genetics*; D014158:Transcription, Genetic / Q000187:drug effects*
D001555:Benzene Derivatives; D016566:Organoselenium Compounds; C061132:diphenyldiselenide; D000623:Porphobilinogen Synthase