Regulation of Schistosoma mansoni development and reproduction by the mitogen-activated protein kinase signaling pathway.
BACKGROUND:Protein kinases are proven targets for drug development with an increasing number of eukaryotic Protein Kinase (ePK) inhibitors now approved as drugs. Mitogen-activated protein kinase (MAPK) family members connect cell-surface receptors to regulatory targets within cells and influence a n...
Published in: | PLoS Neglected Tropical Diseases |
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ftdoajarticles:oai:doaj.org/article:bb2bc265a2c248acad06b47be660594a 2023-05-15T15:09:52+02:00 Regulation of Schistosoma mansoni development and reproduction by the mitogen-activated protein kinase signaling pathway. Luiza Freire de Andrade Marina de Moraes Mourão Juliana Assis Geraldo Fernanda Sales Coelho Larissa Lopes Silva Renata Heisler Neves Angela Volpini José Roberto Machado-Silva Neusa Araujo Rafael Nacif-Pimenta Conor R Caffrey Guilherme Oliveira 2014-06-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0002949 https://doaj.org/article/bb2bc265a2c248acad06b47be660594a EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC4063740?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0002949 https://doaj.org/article/bb2bc265a2c248acad06b47be660594a PLoS Neglected Tropical Diseases, Vol 8, Iss 6, p e2949 (2014) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2014 ftdoajarticles https://doi.org/10.1371/journal.pntd.0002949 2022-12-31T04:01:51Z BACKGROUND:Protein kinases are proven targets for drug development with an increasing number of eukaryotic Protein Kinase (ePK) inhibitors now approved as drugs. Mitogen-activated protein kinase (MAPK) family members connect cell-surface receptors to regulatory targets within cells and influence a number of tissue-specific biological activities such as cell proliferation, differentiation and survival. However, the contributions of members of the MAPK pathway to schistosome development and survival are unclear. METHODOLOGY/PRINCIPAL FINDINGS:We employed RNA interference (RNAi) to elucidate the functional roles of five S. mansoni genes (SmCaMK2, SmJNK, SmERK1, SmERK2 and SmRas) involved in MAPK signaling pathway. Mice were injected with post-infective larvae (schistosomula) subsequent to RNAi and the development of adult worms observed. The data demonstrate that SmJNK participates in parasite maturation and survival of the parasites, whereas SmERK are involved in egg production as infected mice had significantly lower egg burdens with female worms presenting underdeveloped ovaries. Furthermore, it was shown that the c-fos transcription factor was overexpressed in parasites submitted to RNAi of SmERK1, SmJNK and SmCaMK2 indicating its putative involvement in gene regulation in this parasite's MAPK signaling cascade. CONCLUSIONS:We conclude that MAPKs proteins play important roles in the parasite in vivo survival, being essential for normal development and successful survival and reproduction of the schistosome parasite. Moreover SmERK and SmJNK are potential targets for drug development. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLoS Neglected Tropical Diseases 8 6 e2949 |
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Open Polar |
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Directory of Open Access Journals: DOAJ Articles |
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ftdoajarticles |
language |
English |
topic |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
spellingShingle |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Luiza Freire de Andrade Marina de Moraes Mourão Juliana Assis Geraldo Fernanda Sales Coelho Larissa Lopes Silva Renata Heisler Neves Angela Volpini José Roberto Machado-Silva Neusa Araujo Rafael Nacif-Pimenta Conor R Caffrey Guilherme Oliveira Regulation of Schistosoma mansoni development and reproduction by the mitogen-activated protein kinase signaling pathway. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
BACKGROUND:Protein kinases are proven targets for drug development with an increasing number of eukaryotic Protein Kinase (ePK) inhibitors now approved as drugs. Mitogen-activated protein kinase (MAPK) family members connect cell-surface receptors to regulatory targets within cells and influence a number of tissue-specific biological activities such as cell proliferation, differentiation and survival. However, the contributions of members of the MAPK pathway to schistosome development and survival are unclear. METHODOLOGY/PRINCIPAL FINDINGS:We employed RNA interference (RNAi) to elucidate the functional roles of five S. mansoni genes (SmCaMK2, SmJNK, SmERK1, SmERK2 and SmRas) involved in MAPK signaling pathway. Mice were injected with post-infective larvae (schistosomula) subsequent to RNAi and the development of adult worms observed. The data demonstrate that SmJNK participates in parasite maturation and survival of the parasites, whereas SmERK are involved in egg production as infected mice had significantly lower egg burdens with female worms presenting underdeveloped ovaries. Furthermore, it was shown that the c-fos transcription factor was overexpressed in parasites submitted to RNAi of SmERK1, SmJNK and SmCaMK2 indicating its putative involvement in gene regulation in this parasite's MAPK signaling cascade. CONCLUSIONS:We conclude that MAPKs proteins play important roles in the parasite in vivo survival, being essential for normal development and successful survival and reproduction of the schistosome parasite. Moreover SmERK and SmJNK are potential targets for drug development. |
format |
Article in Journal/Newspaper |
author |
Luiza Freire de Andrade Marina de Moraes Mourão Juliana Assis Geraldo Fernanda Sales Coelho Larissa Lopes Silva Renata Heisler Neves Angela Volpini José Roberto Machado-Silva Neusa Araujo Rafael Nacif-Pimenta Conor R Caffrey Guilherme Oliveira |
author_facet |
Luiza Freire de Andrade Marina de Moraes Mourão Juliana Assis Geraldo Fernanda Sales Coelho Larissa Lopes Silva Renata Heisler Neves Angela Volpini José Roberto Machado-Silva Neusa Araujo Rafael Nacif-Pimenta Conor R Caffrey Guilherme Oliveira |
author_sort |
Luiza Freire de Andrade |
title |
Regulation of Schistosoma mansoni development and reproduction by the mitogen-activated protein kinase signaling pathway. |
title_short |
Regulation of Schistosoma mansoni development and reproduction by the mitogen-activated protein kinase signaling pathway. |
title_full |
Regulation of Schistosoma mansoni development and reproduction by the mitogen-activated protein kinase signaling pathway. |
title_fullStr |
Regulation of Schistosoma mansoni development and reproduction by the mitogen-activated protein kinase signaling pathway. |
title_full_unstemmed |
Regulation of Schistosoma mansoni development and reproduction by the mitogen-activated protein kinase signaling pathway. |
title_sort |
regulation of schistosoma mansoni development and reproduction by the mitogen-activated protein kinase signaling pathway. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2014 |
url |
https://doi.org/10.1371/journal.pntd.0002949 https://doaj.org/article/bb2bc265a2c248acad06b47be660594a |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 8, Iss 6, p e2949 (2014) |
op_relation |
http://europepmc.org/articles/PMC4063740?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0002949 https://doaj.org/article/bb2bc265a2c248acad06b47be660594a |
op_doi |
https://doi.org/10.1371/journal.pntd.0002949 |
container_title |
PLoS Neglected Tropical Diseases |
container_volume |
8 |
container_issue |
6 |
container_start_page |
e2949 |
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1766340967237943296 |