Data/hora: 01/06/2024 05:46:01

Provedor de dados: | 5
País: | France
Título: | The anti-fecundity effect of 5-azacytidine (5-AzaC) on Schistosoma mansoni is linked to dis-regulated transcription, translation and stem cell activities
Autores: | Geyer, Kathrin K.; Munshi, Sabrina E.; Vickers, Martin; Squance, Michael; Wilkinson, Toby J.; Berrar, Daniel; Chaparro, Cristian; Swain, Martin T.; Hoffmann, Karl F.
Data: | 2018-08
Ano: | 2018
Palavras-chave: | Schistosoma mansoni; Epigenetics; 5-Azacytidine; Fecundity; RNA-Seq; Protein synthesis; Stem cells.
Resumo: | Uncontrolled host immunological reactions directed against tissue-trapped eggs precipitate a potentially lethal, pathological cascade responsible for schistosomiasis. Blocking schistosome egg production, therefore, presents a strategy for simultaneously reducing immunopathology as well as limiting disease transmission in endemic or emerging areas. We recently demonstrated that the ribonucleoside analogue 5-azacytidine (5-AzaC) inhibited Schistosoma mansoni oviposition, egg maturation and ovarian development. While these anti-fecundity effects were associated with a loss of DNA methylation, other molecular processes affected by 5-AzaC were not examined at the time. By comparing the transcriptomes of 5-AzaC-treated females to controls, we provide evidence that this ribonucleoside analogue also modulates other crucial aspects of schistosome egg-laying biology. For example, S. mansoni gene products associated with amino acid-, carbohydrate-, fatty acid-, nucleotide-and tricarboxylic acid (TCA)-homeostasis are all dysregulated in 5-AzaC treated females. To validate the metabolic pathway most significantly affected by 5-AzaC, amino acid metabolism, nascent protein synthesis was subsequently quantified in adult schistosomes. Here, 5-AzaC inhibited this process by 68% +/- 16.7% (SEM) in maleand 81% +/- 4.8% (SEM) in female-schistosomes. Furthermore, the transcriptome data indicated that adult female stem cells were also affected by 5-AzaC. For instance, 40% of transcripts associated with proliferating schistosome cells were significantly down-regulated by 5-AzaC. This finding correlated with a considerable reduction (95%) in the number of 5-ethynyl-2'-deoxyuridine (EdU) positive cells found in 5-AzaC-treated females. In addition to protein coding genes, the effect that 5-AzaC had on repetitive element expression was also assessed. Here, 46 repeats were found differentially transcribed between 5-AzaC-treated and control females with long terminal repeat (LTR) and DNA transposon classes being amongst the most significant. This study demonstrates that the anti-fecundity activity of 5-AzaC affects more than just DNA methylation in schistosome parasites. Further characterisation of these processes may reveal novel targets for schistosomiasis control.
Tipo: | Text
Idioma: | Inglês

Identificador:

https://archimer.ifremer.fr/doc/00615/72703/71747.pdf

https://archimer.ifremer.fr/doc/00615/72703/71748.xml

https://archimer.ifremer.fr/doc/00615/72703/71749.xlsx

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https://archimer.ifremer.fr/doc/00615/72703/71755.pdf

https://archimer.ifremer.fr/doc/00615/72703/71756.pdf

DOI:10.1016/j.ijpddr.2018.03.006

https://archimer.ifremer.fr/doc/00615/72703/

Editor: | Elsevier Sci Ltd
Formato: | application/pdf
Fonte: | International Journal For Parasitology-drugs And Drug Resistance (2211-3207) (Elsevier Sci Ltd), 2018-08 , Vol. 8 , N. 2 , P. 213-222

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info:eu-repo/semantics/openAccess

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