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Molecular characterisation of a NADH ubiquinone oxidoreductase subunit 5 from Schistosoma mansoni and inhibition of mitochondrial respiratory chain function by testosterone

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Abstract

Complementary DNA, encoding the mitochondrial enzyme NADH-ubiquinone oxidoreductase subunit 5 (SmND5) of the human parasite Schistosoma mansoni was isolated by screening an S. mansoni cDNA library with a human androgen receptor (hAR) cDNA probe. The complete nucleotide and deduced aminoacid sequences of SmND5 were determined. Southern blot analysis revealed the occurrence of a single copy gene for SmND5 and by means of RT-PCR, it was shown that sex- and stage-specific expression of SmND5 occurred. In order to establish a functional relationship between the mitochondrial enzyme and the androgen receptor, the effects of testosterone were compared to those of classical respiratory chain inhibitors, using adult schistosome and beef heart submitochondrial particles. Physiological concentrations of testosterone were able to inhibit the maintenance of proton gradient across the mitochondrial membranes, as well as ATP synthesis. The steroid was found to be cytotoxic to the larvae, but not to adult schistosomes. A model is proposed to explain the observed in vivo testosterone-related differences in worm burdens, in experimental chronic infections.

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Authors and Affiliations

  1. Departamento de Bioquiacute;mica Médica ICB/CCS, Universidade Federal do Rio de Janeiro-Ilha do Fundão, CEP 21941-590, Rio de Janeiro, Brasil

    Marcelo Rosado Fantappié, Antônio Galina, Daniel Rodrigues Furtado, Antônio Jorge Tempone, Lia Lannes de Camargo & Franklin David Rumjanek

  2. Centre D'Immunologie et de Biologie Parasitaire, INSERM U167, Institut Pasteur de Lille, 1, Rue du Professeur A. Calmette, 59 019, Lille, France

    Ricardo Luís de Mendonça

  3. Division of Parasitic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA, 30341, USA

    W. Evan Secor, Daniel G. Colley & George Freeman Jr

  4. Centro de Pesquisas René Rachou- Ministério de Saú, Brazil

    Rodrigo Corrêa-Oliveira

Authors
  1. Marcelo Rosado Fantappié
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  2. Antônio Galina
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  3. Ricardo Luís de Mendonça
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  4. Daniel Rodrigues Furtado
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  5. W. Evan Secor
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  6. Daniel G. Colley
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  7. Rodrigo Corrêa-Oliveira
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  8. George Freeman Jr
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  9. Antônio Jorge Tempone
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  10. Lia Lannes de Camargo
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  11. Franklin David Rumjanek
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Fantappié, M.R., Galina, A., de Mendonça, R.L. et al. Molecular characterisation of a NADH ubiquinone oxidoreductase subunit 5 from Schistosoma mansoni and inhibition of mitochondrial respiratory chain function by testosterone. Mol Cell Biochem 202, 149–158 (1999). https://doi.org/10.1023/A:1007057903390

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  • DOI: https://doi.org/10.1023/A:1007057903390

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