Caspase dependent programmed cell death in developing embryos: a potential target for therapeutic intervention against pathogenic nematodes.
BACKGROUND: Successful embryogenesis is a critical rate limiting step for the survival and transmission of parasitic worms as well as pathology mediated by them. Hence, blockage of this important process through therapeutic induction of apoptosis in their embryonic stages offers promise for developi...
Published in: | PLoS Neglected Tropical Diseases |
---|---|
Main Authors: | , , , |
Format: | Article in Journal/Newspaper |
Language: | English |
Published: |
Public Library of Science (PLoS)
2011
|
Subjects: | |
Online Access: | https://doi.org/10.1371/journal.pntd.0001306 https://doaj.org/article/69654c7d76bb49889b556715b61de464 |
id |
ftdoajarticles:oai:doaj.org/article:69654c7d76bb49889b556715b61de464 |
---|---|
record_format |
openpolar |
spelling |
ftdoajarticles:oai:doaj.org/article:69654c7d76bb49889b556715b61de464 2023-05-15T15:14:37+02:00 Caspase dependent programmed cell death in developing embryos: a potential target for therapeutic intervention against pathogenic nematodes. Alok Das Mohapatra Sunil Kumar Ashok Kumar Satapathy Balachandran Ravindran 2011-09-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0001306 https://doaj.org/article/69654c7d76bb49889b556715b61de464 EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC3172199?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0001306 https://doaj.org/article/69654c7d76bb49889b556715b61de464 PLoS Neglected Tropical Diseases, Vol 5, Iss 9, p e1306 (2011) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2011 ftdoajarticles https://doi.org/10.1371/journal.pntd.0001306 2022-12-31T16:25:45Z BACKGROUND: Successful embryogenesis is a critical rate limiting step for the survival and transmission of parasitic worms as well as pathology mediated by them. Hence, blockage of this important process through therapeutic induction of apoptosis in their embryonic stages offers promise for developing effective anti-parasitic measures against these extra cellular parasites. However, unlike in the case of protozoan parasites, induction of apoptosis as a therapeutic approach is yet to be explored against metazoan helminth parasites. METHODOLOGY/PRINCIPAL FINDINGS: For the first time, here we developed and evaluated flow cytometry based assays to assess several conserved features of apoptosis in developing embryos of a pathogenic filarial nematode Setaria digitata, in-vitro as well as ex-vivo. We validated programmed cell death in developing embryos by using immuno-fluorescence microscopy and scoring expression profile of nematode specific proteins related to apoptosis [e.g. CED-3, CED-4 and CED-9]. Mechanistically, apoptotic death of embryonic stages was found to be a caspase dependent phenomenon mediated primarily through induction of intracellular ROS. The apoptogenicity of some pharmacological compounds viz. DEC, Chloroquine, Primaquine and Curcumin were also evaluated. Curcumin was found to be the most effective pharmacological agent followed by Primaquine while Chloroquine displayed minimal effect and DEC had no demonstrable effect. Further, demonstration of induction of apoptosis in embryonic stages by lipid peroxidation products [molecules commonly associated with inflammatory responses in filarial disease] and demonstration of in-situ apoptosis of developing embryos in adult parasites in a natural bovine model of filariasis have offered a framework to understand anti-fecundity host immunity operational against parasitic helminths. CONCLUSIONS/SIGNIFICANCE: Our observations have revealed for the first time, that induction of apoptosis in developing embryos can be a potential approach for therapeutic ... Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLoS Neglected Tropical Diseases 5 9 e1306 |
institution |
Open Polar |
collection |
Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
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 Alok Das Mohapatra Sunil Kumar Ashok Kumar Satapathy Balachandran Ravindran Caspase dependent programmed cell death in developing embryos: a potential target for therapeutic intervention against pathogenic nematodes. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
BACKGROUND: Successful embryogenesis is a critical rate limiting step for the survival and transmission of parasitic worms as well as pathology mediated by them. Hence, blockage of this important process through therapeutic induction of apoptosis in their embryonic stages offers promise for developing effective anti-parasitic measures against these extra cellular parasites. However, unlike in the case of protozoan parasites, induction of apoptosis as a therapeutic approach is yet to be explored against metazoan helminth parasites. METHODOLOGY/PRINCIPAL FINDINGS: For the first time, here we developed and evaluated flow cytometry based assays to assess several conserved features of apoptosis in developing embryos of a pathogenic filarial nematode Setaria digitata, in-vitro as well as ex-vivo. We validated programmed cell death in developing embryos by using immuno-fluorescence microscopy and scoring expression profile of nematode specific proteins related to apoptosis [e.g. CED-3, CED-4 and CED-9]. Mechanistically, apoptotic death of embryonic stages was found to be a caspase dependent phenomenon mediated primarily through induction of intracellular ROS. The apoptogenicity of some pharmacological compounds viz. DEC, Chloroquine, Primaquine and Curcumin were also evaluated. Curcumin was found to be the most effective pharmacological agent followed by Primaquine while Chloroquine displayed minimal effect and DEC had no demonstrable effect. Further, demonstration of induction of apoptosis in embryonic stages by lipid peroxidation products [molecules commonly associated with inflammatory responses in filarial disease] and demonstration of in-situ apoptosis of developing embryos in adult parasites in a natural bovine model of filariasis have offered a framework to understand anti-fecundity host immunity operational against parasitic helminths. CONCLUSIONS/SIGNIFICANCE: Our observations have revealed for the first time, that induction of apoptosis in developing embryos can be a potential approach for therapeutic ... |
format |
Article in Journal/Newspaper |
author |
Alok Das Mohapatra Sunil Kumar Ashok Kumar Satapathy Balachandran Ravindran |
author_facet |
Alok Das Mohapatra Sunil Kumar Ashok Kumar Satapathy Balachandran Ravindran |
author_sort |
Alok Das Mohapatra |
title |
Caspase dependent programmed cell death in developing embryos: a potential target for therapeutic intervention against pathogenic nematodes. |
title_short |
Caspase dependent programmed cell death in developing embryos: a potential target for therapeutic intervention against pathogenic nematodes. |
title_full |
Caspase dependent programmed cell death in developing embryos: a potential target for therapeutic intervention against pathogenic nematodes. |
title_fullStr |
Caspase dependent programmed cell death in developing embryos: a potential target for therapeutic intervention against pathogenic nematodes. |
title_full_unstemmed |
Caspase dependent programmed cell death in developing embryos: a potential target for therapeutic intervention against pathogenic nematodes. |
title_sort |
caspase dependent programmed cell death in developing embryos: a potential target for therapeutic intervention against pathogenic nematodes. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2011 |
url |
https://doi.org/10.1371/journal.pntd.0001306 https://doaj.org/article/69654c7d76bb49889b556715b61de464 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 5, Iss 9, p e1306 (2011) |
op_relation |
http://europepmc.org/articles/PMC3172199?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0001306 https://doaj.org/article/69654c7d76bb49889b556715b61de464 |
op_doi |
https://doi.org/10.1371/journal.pntd.0001306 |
container_title |
PLoS Neglected Tropical Diseases |
container_volume |
5 |
container_issue |
9 |
container_start_page |
e1306 |
_version_ |
1766345055387254784 |