Journal
INTERNATIONAL JOURNAL FOR PARASITOLOGY
Volume 40, Issue 8, Pages 929-935Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.ijpara.2010.01.001
Keywords
Schistosoma mansoni; Schistosome; Blood fluke; Protein kinase A; Parasite development; Reproductive biology
Categories
Funding
- National Institutes of Health/National Institute of Allergy and Infectious Diseases (USA) [N01 AI30026]
- National Institutes of Health/National Institute of Allergy and Infectious Diseases [R01 AI066227]
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cAMP-dependent protein kinases (PKAs) are the main transducers of cAMP signalling in eukaryotic cells. Recently we reported the identification and characterisation of a PKA catalytic subunit (SmPKA-C) in Schistosoma mansoni that is required for adult schistosome viability in vitro. To gain further insights into the role of SmPKA-C in biological processes during the schistosome life cycle, we undertook a quantitative analysis of SmPKA-C mRNA expression in different life cycle stages. Our data shows that SmPKA-C mRNA expression is developmentally regulated, with the highest levels of expression in cercariae and adult female worms. To evaluate the biological role of SmPKA-C in these developmental stages, cercariae and adult worms were treated with various concentrations of PKA inhibitors. Treatment of cercariae with H-89 or PKI 14-22 amide resulted in loss of viability suggesting that, as in adults. PKA is an essential enzyme activity in this infectious larval stage. In adult worms, in vitro exposure to sub-lethal concentrations of H-89 or PKI 14-22 amide resulted in inhibition of egg production in a dose-dependent manner. Furthermore, using a murine model of schistosome infection where S. mansoni fecundity is impaired, we show that reduced rates of egg production in vivo correlate with significant reductions in SmPKA-C mRNA expression and PKA activity. Finally, restoration of parasite egg production in vivo also resulted in normalisation of SmPKA-C mRNA expression and PKA activity. Taken together, our data suggest that PKA signalling is required for cercarial viability and may play a specific role in the reproductive activity of adult worms. Published by Elsevier Ltd. on behalf of Australian Society for Parasitology Inc.
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