المؤلفون: Lu Zhao, Xin He, Christoph G. Grevelding, Qing Ye, Ying Li, Robin B. Gasser, Colette Dissous, Mudassar N. Mughal, Yan-Qin Zhou, Jun-Long Zhao, Min Hu

المصدر: Parasites & Vectors, Vol 10, Iss 1, Pp 1-15 (2017)

مصطلحات موضوعية: Schistosoma japonicum, RIO2 kinase, RNA interference, Gonad, Reproductive development, Infectious and parasitic diseases, RC109-216

الوصف: Abstract Background Schistosomiasis is one of the most prevalent parasitic diseases worldwide and is caused by parasitic trematodes of the genus Schistosoma. The pathogenesis of schistosomiasis is caused by eggs whose production is the consequence of the pairing of schistosomes and the subsequent sexual maturation of the female. Previous studies have demonstrated that protein kinases are involved in processes leading to the male-induced differentiation of the female gonads, ovary and vitellarium. Right open reading frame protein kinase 2 (RIOK-2) is a member of the atypical kinase family and shown in other organisms to be responsible for ribosomal RNA biogenesis and cell-cycle progression, as well as involves in nematode development. However, nothing is known about its functions in any trematode including schistosome. Methods We isolated and characterized the riok-2 gene from S. japonicum, and detected the transcriptional profiles of Sj-riok-2 by using real-time PCR and in situ hybridization. RNAi-mediated knockdown of Sj-riok-2 was performed, mitotic activities were detected by EdU incorporation assay and morphological changes on organs were observed by confocal laser scanning microscope (CLSM). Results In silico analyses of the amino acid sequence of Sj-RIOK-2 revealed typical features of this class of kinases including a winged helix (wHTH) domain and a RIO kinase domain. Sj-riok-2 is transcribed in different developmental stages of S. japonicum, with a higher abundance in adult females and eggs. Localization studies showed that Sj-riok-2 was mainly transcribed in female reproductive organs. Experiments with adult schistosomes in vitro demonstrated that the transcriptional level of Sj-riok-2 was affected by pairing. Knocking down Sj-riok-2 by RNAi reduced cell proliferation in the vitellarium and caused the increased amount of mature oocytes in ovary and an accumulation of eggs within the uterus. Conclusions Sj-riok-2 is involved in the reproductive development and maturation of female S. japonicum. Our findings provide first evidence for a pairing-dependent role of Sj-riok-2 in the reproductive development and maturation of female S. japonicum. Thus this study contributes to the understanding of molecular processes controlling reproduction in schistosomes.

وصف الملف: electronic resource

العلاقة: http://link.springer.com/article/10.1186/s13071-017-2524-7Test; https://doaj.org/toc/1756-3305Test

الوصول الحر: https://doaj.org/article/6d30054a0bbd4408af79cedf135ee64bTest

المؤلفون: Mudassar N. Mughal, Qing Ye, Lu Zhao, Christoph G. Grevelding, Ying Li, Wenda Di, Xin He, Xuesong Li, Robin B. Gasser, Min Hu

المصدر: Pathogens, Vol 10, Iss 7, p 862 (2021)

مصطلحات موضوعية: schistosomiasis, Schistosoma japonicum, right open reading frame protein kinase (riok) genes, riok-1, RIOK-1, double-stranded RNA interference (RNAi), Medicine

الوصف: Protein kinases are known as key molecules that regulate many biological processes in animals. The right open reading frame protein kinase (riok) genes are known to be essential regulators in model organisms such as the free-living nematode Caenorhabditis elegans. However, very little is known about their function in parasitic trematodes (flukes). In the present study, we characterized the riok-1 gene (Sj-riok-1) and the inferred protein (Sj-RIOK-1) in the parasitic blood fluke, Schistosoma japonicum. We gained a first insight into function of this gene/protein through double-stranded RNA interference (RNAi) and chemical inhibition. RNAi significantly reduced Sj-riok-1 transcription in both female and male worms compared with untreated control worms, and subtle morphological alterations were detected in the ovaries of female worms. Chemical knockdown of Sj-RIOK-1 with toyocamycin (a specific RIOK-1 inhibitor/probe) caused a substantial reduction in worm viability and a major accumulation of mature oocytes in the seminal receptacle (female worms), and of spermatozoa in the sperm vesicle (male worms). These phenotypic alterations indicate that the function of Sj-riok-1 is linked to developmental and/or reproductive processes in S. japonicum.

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/2076-0817/10/7/862Test; https://doaj.org/toc/2076-0817Test

الوصول الحر: https://doaj.org/article/c139b40b42c34caf9b026945fcd45217Test

المؤلفون: Simone Haeberlein, Mudassar N. Mughal, Christoph G. Grevelding

المصدر: International Journal for Parasitology. 52:211-215

مصطلحات موضوعية: Drug, media_common.quotation_subject, Antineoplastic Agents, Schistosomiasis, Biology, Pharmacology, Praziquantel, hemic and lymphatic diseases, parasitic diseases, Autophagy, medicine, Animals, media_common, Tropical disease, Imatinib, Schistosoma mansoni, medicine.disease, biology.organism_classification, Schistosomiasis mansoni, In vitro, Infectious Diseases, Imatinib Mesylate, Parasitology, medicine.drug

الوصف: Schistosomiasis, caused by schistosome parasites, is a neglected tropical disease affecting humans and animals. There is no vaccine available yet, and fear of upcoming resistance against the only widely used drug, praziquantel, is omnipresent. Previously, we showed that imatinib (Gleevec), an anticancer drug, affected schistosome physiology and caused the death of adult Schistosoma mansoni in vitro. Here, we present the first known evidence that one effect of imatinib is the induction of autophagy in S. mansoni. Furthermore, worms co-treated with imatinib and bafilomycin A1, a late-phase autophagy inhibitor, reversed imatinib-induced autophagy and its antischistosomal effects as revealed by phenotypic and molecular analyses.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3fb8a93ac022803503b6f13aff529bbcTest
https://doi.org/10.1016/j.ijpara.2021.10.008Test

المؤلفون: Xuesong Li, Ying Li, Min Hu, Wenda Di, Robin B. Gasser, Christoph G. Grevelding, Qing Ye, Mudassar N. Mughal, Xin He, Lu Zhao

المصدر: Pathogens
Volume 10
Issue 7
Pathogens, Vol 10, Iss 862, p 862 (2021)

مصطلحات موضوعية: 0301 basic medicine, Microbiology (medical), 030231 tropical medicine, ved/biology.organism_classification_rank.species, developmental and reproductive biology, 03 medical and health sciences, 0302 clinical medicine, right open reading frame protein kinase (riok) genes, RNA interference, schistosomiasis, toyocamycin, parasitic diseases, Immunology and Allergy, Model organism, Protein kinase A, Molecular Biology, Gene, Schistosoma japonicum, Schistosoma, Gene knockdown, General Immunology and Microbiology, biology, ved/biology, riok-1, chemical inhibition, biology.organism_classification, RIOK-1, Cell biology, Open reading frame, 030104 developmental biology, Infectious Diseases, Medicine, double-stranded RNA interference (RNAi)

الوصف: Protein kinases are known as key molecules that regulate many biological processes in animals. The right open reading frame protein kinase (riok) genes are known to be essential regulators in model organisms such as the free-living nematode Caenorhabditis elegans. However, very little is known about their function in parasitic trematodes (flukes). In the present study, we characterized the riok-1 gene (Sj-riok-1) and the inferred protein (Sj-RIOK-1) in the parasitic blood fluke, Schistosoma japonicum. We gained a first insight into function of this gene/protein through double-stranded RNA interference (RNAi) and chemical inhibition. RNAi significantly reduced Sj-riok-1 transcription in both female and male worms compared with untreated control worms, and subtle morphological alterations were detected in the ovaries of female worms. Chemical knockdown of Sj-RIOK-1 with toyocamycin (a specific RIOK-1 inhibitor/probe) caused a substantial reduction in worm viability and a major accumulation of mature oocytes in the seminal receptacle (female worms), and of spermatozoa in the sperm vesicle (male worms). These phenotypic alterations indicate that the function of Sj-riok-1 is linked to developmental and/or reproductive processes in S. japonicum.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3c21a60e729ea1b8f2908010363f840cTest

المؤلفون: Christoph G. Grevelding, Mudassar N. Mughal, Simone Haeberlein

المصدر: International Journal for Parasitology.

مصطلحات موضوعية: Male, 0301 basic medicine, In silico, 030231 tropical medicine, Cellular homeostasis, Biology, Real-Time Polymerase Chain Reaction, Wortmannin, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, parasitic diseases, Autophagy, Animals, Gene, Bafilomycin, Schistosoma mansoni, biology.organism_classification, Schistosomiasis mansoni, In vitro, Cell biology, 030104 developmental biology, Infectious Diseases, chemistry, Female, Parasitology

الوصف: Schistosomiasis is a disease of global importance caused by parasitic flatworms, schistosomes, which cause pathogenicity through eggs laid by the female worm inside the host's blood vessels. Maintenance of cellular homeostasis is crucial for parasites, as for other organisms, and is quite likely important for schistosome reproduction and vitality. We hypothesize a role for autophagy in these processes, an evolutionarily conserved and essential cellular degradation pathway. Here, for the first known time, we shed light on the autophagy machinery and its involvement in pairing-dependent processes, vitality and reproduction of Schistosoma mansoni. We identified autophagy genes by in silico analyses and determined the influence of in vitro culture on the transcriptional expression in male and female worms using quantitative real-time PCR. Among the identified autophagy genes were Beclin, Ambra1, Vps34, DRAM, DAP1, and LC3B, of which some showed a sex-dependent expression. Specifically, the death-associated protein DAP1 was significantly more highly expressed in females compared with males, while for the damage-regulated autophagy modulator DRAM it was the opposite. Furthermore, in-vitro culture significantly changed the transcript expression level of DAP1 in female worms. Next, worms were treated with an autophagy inducer (rapamycin) or inhibitors (bafilomycin A1, wortmannin and spautin-1) to evaluate effects on autophagy protein expression, worm vitality, and reproduction. The conversion of the key autophagy protein LC3B, a marker for autophagic activity, was increased by rapamycin and blocked by bafilomycin. All inhibitors affected worm fitness, egg production, and negatively affected the morphology of gonads and intestine. In summary, autophagy genes in S. mansoni show an interesting sex-dependent expression pattern and manipulation of autophagy in S. mansoni by inhibitors induced detrimental effects, which encourages subsequent studies to identify antischistosomal targets within the autophagy machinery.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3b728bf0189f9a9e6adc9cb35c0d4102Test
https://doi.org/10.1016/j.ijpara.2020.11.011Test