Prostaglandin D(2) synthesis in Oesophagostomum dentatum is mediated by cytosolic glutathione S-transferase.
Glutathione S-transferases (GSTs) of Oesophagostomum dentatum possess considerable similarity to synthetic prostaglandin D synthase (PGDS), and therefore their ability to convert prostaglandin (PG) H(2) to PGD(2)in vitro was investigated with a commercial Prostaglandin D Synthase Inhibitor Screening Assay Kit. Fractioned homogenates of O. dentatum third-stage larvae only displayed cytosolic but not microsomal GST. Both total larval homogenate and isolated GST could metabolise PGH(2) to PGD(2), which could be inhibited by the GST inhibitor sulfobromophthalein (SBP) in a dose-dependent manner, whereas reactions to the specific PGDS inhibitor HQL-79 were not dose-dependent. Inhibition of larval development by SBP in vitro was abolished by the addition of PGD(2) but not by PGH(2), supporting the assumption that GST acts as PGDS and is important for nematode development. Since motility and viability of O. dentatum larvae are reduced in vitro by various inhibitors of eicosanoid metabolism, enzymes of this pathway, including GST, constitute putative intervention targets.
Institute of Parasitology, University of Veterinary Medicine Vienna, Veterinaerplatz 1, A-1210 Vienna, Austria. Anja.Joachim@vetmeduni.ac.at
Anja
A
Joachim
Bärbel
B
Ruttkowski
D000818:Animals; D003600:Cytosol / Q000201:enzymology; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D005982:Glutathione Transferase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007124:Immunoenzyme Techniques; D007202:Indicators and Reagents; D007814:Larva / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D008861:Microsomes / Q000201:enzymology; D009815:Oesophagostomum / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D010880:Piperidines / Q000494:pharmacology; D015230:Prostaglandin D2 / Q000096:biosynthesis*; D044262:Prostaglandin H2 / Q000378:metabolism; D013448:Sulfobromophthalein / Q000494:pharmacology
C116322:4-benzhydryloxy-1-(3-(1H-tetrazol-5-yl-)-propyl)piperidine; D007202:Indicators and Reagents; D010880:Piperidines; D013448:Sulfobromophthalein; D044262:Prostaglandin H2; D005982:Glutathione Transferase; D015230:Prostaglandin D2