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

Complementary DNA, encoding the mitochondrial enzyme NADH-ubiquinone oxidor eductase subunit 5 (SmND5) of the human parasite Schistosoma mansoni was is olated by screening a S. mansoni cDNA library with a human androgen recepto r (hAR) cDNA probe. The complete nucleotide and deduced aminoacid sequences of SmND5 were determined. Southern blot analysis revealed the occurrence o f a single copy gene for SmND5 and by means of RT-PCR, it was shown that se x- 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 r espiratory chain inhibitors, using adult schistosome and beef heart submito chondrial particles. Physiological concentrations of testosterone were able to inhibit the maintenance of proton gradient across the mitochondrial mem branes, 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 t he observed in vivo testosterone-related differences in worm burdens, in ex perimental chronic infections.