Oltipraz-induced decrease in the activity of cytosolic glutathione S-transferase in Schistosoma mansoni.
The activity of glutathione S-transferase (GST) decreased progressively in Schistosoma mansoni from mice treated with oltipraz (OPZ). However, the peroxidase activity of GST (selenium-independent) and selenium-dependent glutathione peroxidase was not affected by OPZ treatment. Purification and quantification of GST from worms after OPZ treatment indicated that the decrease in enzyme activity was greater than could be accounted for by the decrease in GST protein content. SDS-polyacrylamide gel electrophoresis followed by Western blot analysis with GST isoenzyme specific antisera revealed a slight decrease in the quantity of both 26 and 28 kDa GSTs. Fractionation of cytosolic GSTs from male S. mansoni by chromatofocusing resolved three major isoenzymes (SmI, II and III) and a minor form which eluted first from the column. SmI, II and III all had a molecular weight of about 28 kDa on SDS-polyacrylamide gel electrophoresis. However, on electrophoresis in the absence of SDS, the three GST forms exhibited different mobilities. The pattern of SmI, II and III was similar in untreated and OPZ-treated worms, but the activities of the isoenzymes from treated worms were lower. The results suggest that OPZ interacts with the GST isoenzymes SmI, II and III in a similar manner; thus, the effects are not isoenzyme specific. Taken together, these results suggest that OPZ and/or its metabolites interact directly with GST resulting in inhibition of activity and reduction in total enzyme protein. This mechanism may be important in the antischistosomal action of OPZ.
Nare
B
B
Institute of Parasitology, McGill University, Ste-Anne de Bellevue, Québec, Canada.
Smith
J M
JM
Prichard
R K
RK
D000818:Animals; D003600:Cytosol / Q000201:enzymology; D005979:Glutathione Peroxidase / Q000187:drug effects; D005982:Glutathione Transferase / Q000187:drug effects*; D007527:Isoenzymes / Q000187:drug effects*; D008297:Male; D011719:Pyrazines / Q000494:pharmacology*; D012550:Schistosoma mansoni / Q000187:drug effects* / Q000201:enzymology; D012556:Schistosomicides / Q000494:pharmacology*; D013871:Thiones; D013876:Thiophenes
D007527:Isoenzymes; D011719:Pyrazines; D012556:Schistosomicides; D013871:Thiones; D013876:Thiophenes; C026209:oltipraz; D005979:Glutathione Peroxidase; D005982:Glutathione Transferase