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Original Article

Identification of a Novel Prostaglandin F₂ Synthase in Trypanosoma brucei

^a Department of Molecular Behavioral Biology, Osaka Bioscience Institute, Osaka 565-0874, Japan
^b Physiologisch-chemisches Institut der Universität Tübingen, 72076 Tübingen, Germany
^c Department of Molecular Protozoology, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan
^d Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation, Tsukuba 305-8575, Japan
^e Department of Parasitology, National Institute of Infectious Diseases, Tokyo 162-8640, Japan
^f Research and Development Division, Pharmaceuticals Group, Nippon Kayaku Company, Limited, Tokyo 102-8172, Japan
Dept. of Molecular Behavioral Biology, Osaka Bioscience Institute, 6-2-4 Furuedai, Suita, Osaka 565-0874, Japan.81-6-6872-284181-6-6872-4851

Members of the genus Trypanosoma cause African trypanosomiasis in humans and animals in Africa. Infection of mammals by African trypanosomes is characterized by an upregulation of prostaglandin (PG) production in the plasma and cerebrospinal fluid. These metabolites of arachidonic acid (AA) may, in part, be responsible for symptoms such as fever, headache, immunosuppression, deep muscle hyperaesthesia, miscarriage, ovarian dysfunction, sleepiness, and other symptoms observed in patients with chronic African trypanosomiasis. Here, we show that the protozoan parasite T. brucei is involved in PG production and that it produces PGs enzymatically from AA and its metabolite, PGH₂. Among all PGs synthesized, PGF₂ was the major prostanoid produced by trypanosome lysates. We have purified a novel T. brucei PGF₂ synthase (TbPGFS) and cloned its cDNA. Phylogenetic analysis and molecular properties revealed that TbPGFS is completely distinct from mammalian PGF synthases. We also found that TbPGFS mRNA expression and TbPGFS activity were high in the early logarithmic growth phase and low during the stationary phase. The characterization of TbPGFS and its gene in T. brucei provides a basis for the molecular analysis of the role of parasite-derived PGF₂ in the physiology of the parasite and the pathogenesis of African trypanosomiasis.

Key Words: Trypanosoma brucei • African trypanosomiasis • PG production • PGF₂ synthase • aldo-keto reductase

© 2000 The Rockefeller University Press

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