Functional Specific Binding of Testosterone toSchistosoma haematobium28-Kilodalton GlutathioneS-Transferase
| Autor: | Anne-Marie Schacht, André Capron, Martine Pugnière, Gilles Riveau, Jean-Claude Mani, Franck Remoue |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
medicine.medical_specialty
medicine.drug_class Recombinant Fusion Proteins Immunology Microbiology Schistosomiasis haematobia Immune system Internal medicine medicine Animals Testosterone Functional ability Nippostrongylus brasiliensis Glutathione Transferase Schistosoma Binding Sites biology Helminth Proteins Androgen biology.organism_classification Infectious Diseases Glutathione S-transferase Endocrinology Antigens Helminth Schistosoma haematobium biology.protein Parasitology Schistosoma mansoni Fungal and Parasitic Infections Peptides Protein Binding Hormone |
| Zdroj: | Infection and Immunity. 70:601-605 |
| ISSN: | 1098-5522 0019-9567 |
| Popis: | Sex hormones seem to have an influence on the level of parasitic infection. Indeed, gender-dependent patterns of prevalence and intensity of infection after puberty have been observed for several parasite species (5). It has been suggested that this effect seems to be associated with the regulatory roles of sex steroids on antiparasite immunity (2, 24). Generally, female hormones have an influence in increasing antibody response against specific antigen, which could explain the higher resistance of women against several parasitic infections (24, 25). During human Schistosoma infection, a chronic infection affecting 200 million individuals around the world, sex hormones and particularly the high level of testosterone after puberty could be an important immune modulator leading to the decrease of susceptibility to infection with age (10, 26). In mice infected by Schistosoma mansoni, fewer adult worms develop in males than in similarly infected females (9). In addition, female mice treated with testosterone before infection presented a reduction in worm burden, whereas no difference in antischistosome immune response was detected between treated and untreated animals (20). These authors suggest thus that effects of testosterone on specific immunity are not adequate to explain the differences in parasite loads observed between the sexes. Schistosomes could express a hormone receptor with homology to the testosterone receptor, which could explain the direct effect of testosterone on worm development (8). Interestingly, it has been demonstrated that testosterone treatment can affect not only the development of Nippostrongylus brasiliensis helminthic worms but also the fecundity and maturity of laid eggs (27). Glutathione S-transferases (GSTs), a family of enzymes, are able to detoxify electrophilic compounds by catalyzing the formation of glutathione conjugates (12). Mammal GSTs are also involved in the intracellular transport of a variety of endogenous metabolites, drugs, and hormones by their abilities to bind these substances (16). Particularly, GSTs are glucocorticoid-binding proteins and, thereby, may influence transport, metabolism, and action of steroids (13). It has also been demonstrated that testosterone and progesterone have the ability to bind mammal GSTs with moderate (10−6 < Kd < 10−4 M) or high (Kd < 10−6 M) affinity, respectively (16). Thus, GSTs are also involved in the transport of sexual steroids and could play a key role in the physiological action of these hormones. The Schistosoma 28-kDa GST (28GST) is an essential enzyme for the parasite life in its host and is now a vaccine candidate against schistosomiasis (6). Immunization with recombinant 28GST Schistosoma haematobium (Sh28GST) has been shown to reduce S. haematobium fecundity in experimentally infected monkeys (4). It is well established in rodents (30) and observed during human infection (11) that this antifecundity effect is associated with the inhibition of the 28GST enzymatic activity by recognation of specific antibodies. Particularly, antibodies directed against amino acids 24 to 43 or 190 to 211 involved in the enzymatic site of the 28GST inhibited the GST activity, reducing tissue egg number and egg viability (31). Ultrastructural localization of antigen in adult worms showed that 28GST was identified in the tegument and the parenchyma, but also in the germinal organ of both male and female parasites (17, 21). These results indicate that 28GST expression seems to be closely associated with parasite metabolism but also with the genital tract, which could explain the relationship between the inhibition of enzymatic activity and an antifecundity effect. The aim of our study was to demonstrate the potential binding of testosterone to Sh28GST and evaluate the functional ability of this binding on the enzymatic activity of the parasite protein. |
| Databáze: | OpenAIRE |
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