title: Schistosome Na,K-ATPase as a therapeutic target.
abstract: Na,K-ATPases are ubiquitous membrane-bound enzymes comprising α and β subunits. Here we clone a Na,K-ATPase β homolog (designated SNaK1β) from the human parasitic platyhelminth, Schistosoma mansoni. The predicted protein is about 33 kDa, and contains a single transmembrane domain and multiple conserved motifs. SNaK1β and its previously cloned α-subunit counterpart (SNaK1α) are both expressed throughout the schistosome life cycle. In adults, both subunits are detected in the tegumental membrane, likely functioning at the host-parasite interface in Na/K exchange. Both SNaK1 genes can be suppressed by RNAi using target-specific small inhibitory RNAs (siRNAs), and this severely debilitates the parasites both in vitro and in vivo. However, treating schistosomiasis by delivering the siRNAs hydrodynamically to infected mice has no detectable impact on worms. Additionally, treating schistosome-infected mice with the Na,K-ATPase inhibitor, ouabain, is ineffective. Nonetheless, since schistosomes are very susceptible to perturbation in SNaK1 expression, further work to identify other Na,K-ATPase inhibitors as anti-schistosome agents is warranted.
authors.affiliation: Molecular Helminthology Laboratory, Department of Biomedical Sciences, Division of Infectious Diseases, Cummings School of Veterinary Medicine, Tufts University, North Grafton, MA, USA.
authors.forename: Akram A
authors.initials: AA
authors.lastname: Da'dara
authors.forename: Zahra
authors.initials: Z
authors.lastname: Faghiri
authors.forename: Greice
authors.initials: G
authors.lastname: Krautz-Peterson
authors.forename: Rita
authors.initials: R
authors.lastname: Bhardwaj
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Skelly
mesh_terms: D000818:Animals; D000871:Anthelmintics / Q000494:pharmacology; D003001:Cloning, Molecular; D015971:Gene Expression Regulation, Enzymologic; D051379:Mice; D021122:Protein Subunits / Q000378:metabolism; D034741:RNA, Small Interfering; D012550:Schistosoma mansoni / Q000201:enzymology*; D012552:Schistosomiasis / Q000188:drug therapy* / Q000235:genetics; D049994:Sodium Potassium Chloride Symporter Inhibitors / Q000494:pharmacology; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000871:Anthelmintics; D021122:Protein Subunits; D034741:RNA, Small Interfering; D049994:Sodium Potassium Chloride Symporter Inhibitors; D000254:Sodium-Potassium-Exchanging ATPase