RESUMO
Opisthorchis felineus is a trematode flatworm that parasitises mammals, including humans, and is mainly spread throughout Eastern Europe and Western Siberia. The main drug used in treatment of opisthorchiasis and other trematode and cestode infestations is praziquantel (PZQ). We provide a possible explanation of PZQ-mediated tegument disruption. The idea is that the nature of tegument disruption is related to failure of surface renovation due to insufficiency of microtubule transport of vesicles. This insufficiency arises from microtubule destabilisation, which in the medium term leads to the decrease in tubulins alpha, beta and dynein mRNA amounts and deficiency of the corresponding proteins. We also found the upregulation of cGMP-dependent protein kinase gene, and we concluded that its protein product helped to overcome the effect of praziquantel and might be a promising target for combined anthelmintic therapy with PZQ. We concluded that function of saposin-like protein 2 (SAP2) is unlikely associated with membrane fusion, and SAP2 is probably able to bind some type of hydrophobic compounds including praziquantel.
Assuntos
Proteínas Quinases Dependentes de GMP Cíclico/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Proteínas de Helminto/genética , Opisthorchis/efeitos dos fármacos , Praziquantel/farmacologia , Animais , Antiplatelmínticos/farmacologia , Antiplatelmínticos/uso terapêutico , Proteínas Quinases Dependentes de GMP Cíclico/antagonistas & inibidores , Humanos , Microtúbulos/efeitos dos fármacos , Microtúbulos/genética , Opistorquíase/tratamento farmacológico , Praziquantel/uso terapêuticoRESUMO
Saposin B domain-containing or saposin-like proteins (SAPs, SAPLIPs) have been described as lipid/membrane-binding and often show antibacterial and cytolytic activity. Members of this protein family are present in phylogenetically distant organisms, pointing to their functional importance. Several SAPs are found in trematodes and some of them apparently are related to host-parasite interaction as they show cytolytic activity or immunogenicity. In the present study, we search for SAP genes of Opisthorchis felineus, Clonorchis sinensis and O. viverrini, compare and analyze their structure and expression patterns. We define three orthologous groups of SAPs in opisthorchids and suggest a unique protein motif with unknown function in one group of orthologs.
