Trypanosome-induced increase in prostaglandin F2α and its relationship with corpus luteum function in the goat

Mutayoba, Benezeth; Meyer, Heinrich; Osaso, J.; Gombe, S.

doi:10.1016/0093-691x(89)90276-8

Cited by 12 publications

(8 citation statements)

References 15 publications

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“…Infection of mammals by African trypanosomes results in the release of high levels of PGs 1617 that may, in part, be involved in the pathogenesis of the disease. It is generally believed and accepted that the PGs are produced by host cells after their stimulation with trypanosome products 5556.…”

Section: Resultsmentioning

confidence: 99%

“…In Schistosoma mansoni , PG production has been reported to be associated with the transformation of cercaria into schistosomules 14, whereas in the protozoan parasite Amoeba proteus , PGs may play a signal-coupling role during phagocytosis, because they elicit vacuole formation 15. PGF 2α and PGD 2 are also found to be consistently elevated in the plasma of animals experimentally infected with Trypanosoma congolense 16 and in the cerebrospinal fluid of humans with chronic infection of T. brucei gambiense 17, respectively. These results suggest an upregulation of PG production during African trypanosomiasis.…”

Section: Introductionmentioning

confidence: 99%

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Identification of a Novel Prostaglandin F2α Synthase in Trypanosoma brucei

Kubata¹,

Duszenko

Kabututu

et al. 2000

The Journal of Experimental Medicine

102

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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, PGF2α was the major prostanoid produced by trypanosome lysates. We have purified a novel T. brucei PGF2α 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 PGF2α in the physiology of the parasite and the pathogenesis of African trypanosomiasis.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Identification of a Novel Prostaglandin F2α Synthase in Trypanosoma brucei

Kubata¹,

Duszenko

Kabututu

et al. 2000

The Journal of Experimental Medicine

102

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“…The gene encoding PGF synthase is present in T. brucei , and we show that this enzyme can be secreted. Given that African trypanosomiasis is characterized by miscarriage, due to PGF overproduction correlated with parasitemia peaks [66], the finding that T. brucei secretes a PGF synthase suggests that this enzyme may well play a role in pathogenesis.…”

Section: Discussionmentioning

confidence: 99%

Exocytosis and protein secretion in Trypanosoma

et al. 2010

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BackgroundHuman African trypanosomiasis is a lethal disease caused by the extracellular parasite Trypanosoma brucei. The proteins secreted by T. brucei inhibit the maturation of dendritic cells and their ability to induce lymphocytic allogenic responses. To better understand the pathogenic process, we combined different approaches to characterize these secreted proteins.ResultsOverall, 444 proteins were identified using mass spectrometry, the largest parasite secretome described to date. Functional analysis of these proteins revealed a strong bias toward folding and degradation processes and to a lesser extent toward nucleotide metabolism. These features were shared by different strains of T. brucei, but distinguished the secretome from published T. brucei whole proteome or glycosome. In addition, several proteins had not been previously described in Trypanosoma and some constitute novel potential therapeutic targets or diagnostic markers. Interestingly, a high proportion of these secreted proteins are known to have alternative roles once secreted. Furthermore, bioinformatic analysis showed that a significant proportion of proteins in the secretome lack transit peptide and are probably not secreted through the classical sorting pathway. Membrane vesicles from secretion buffer and infested rat serum were purified on sucrose gradient and electron microscopy pictures have shown 50- to 100-nm vesicles budding from the coated plasma membrane. Mass spectrometry confirmed the presence of Trypanosoma proteins in these microvesicles, showing that an active exocytosis might occur beyond the flagellar pocket.ConclusionsThis study brings out several unexpected features of the secreted proteins and opens novel perspectives concerning the survival strategy of Trypanosoma as well as possible ways to control the disease. In addition, concordant lines of evidence support the original hypothesis of the involvement of microvesicle-like bodies in the survival strategy allowing Trypanosoma to exchange proteins at least between parasites and/or to manipulate the host immune system.

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“…Infection of mammals by African trypanosomes is characterized by increased levels of PGF 2α and PGD 2 in plasma 355 and CSF, 356 respectively. Kubata et al .…”

Section: Prostaglandin F Synthases (Pgfss)mentioning

confidence: 99%