Profiling molecular factors associated with pyknosis and developmental arrest induced by an opioid receptor antagonist and dihydroartemisinin in Plasmodium falciparum
Malaria continues to be a devastating disease, largely caused by Plasmodium falciparum infection. We investigated the effects of opioid and cannabinoid receptor antagonists on the growth of intraerythrocytic P. falciparum. The delta opioid receptor antagonist 7-benzylidenenaltrexone (BNTX) and the c...
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description | Malaria continues to be a devastating disease, largely caused by Plasmodium falciparum infection. We investigated the effects of opioid and cannabinoid receptor antagonists on the growth of intraerythrocytic P. falciparum. The delta opioid receptor antagonist 7-benzylidenenaltrexone (BNTX) and the cannabinoid receptor antagonists rimonaband and SR144528 caused growth arrest of the parasite. Notably BNTX and the established antimalarial drug dihydroartemisinin induced prominent pyknosis in parasite cells after a short period of incubation. We compared genome-wide transcriptome profiles in P. falciparum with different degrees of pyknosis in response to drug treatment, and identified 11 transcripts potentially associated with the evoking of pyknosis, of which three, including glutathione reductase (PfGR), triose phosphate transporter (PfoTPT), and a conserved Plasmodium membrane protein, showed markedly different gene expression levels in accordance with the degree of pyknosis. Furthermore, the use of specific inhibitors confirmed PfGR but not PfoTPT as a possible factor contributing to the development of pyknosis. A reduction in total glutathione levels was also detected in association with increased pyknosis. These results further our understanding of the mechanisms responsible for P. falciparum development and the antimalarial activity of dihydroartemisinin, and provide useful information for the development of novel antimalarial agents. |
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We investigated the effects of opioid and cannabinoid receptor antagonists on the growth of intraerythrocytic P. falciparum. The delta opioid receptor antagonist 7-benzylidenenaltrexone (BNTX) and the cannabinoid receptor antagonists rimonaband and SR144528 caused growth arrest of the parasite. Notably BNTX and the established antimalarial drug dihydroartemisinin induced prominent pyknosis in parasite cells after a short period of incubation. We compared genome-wide transcriptome profiles in P. falciparum with different degrees of pyknosis in response to drug treatment, and identified 11 transcripts potentially associated with the evoking of pyknosis, of which three, including glutathione reductase (PfGR), triose phosphate transporter (PfoTPT), and a conserved Plasmodium membrane protein, showed markedly different gene expression levels in accordance with the degree of pyknosis. Furthermore, the use of specific inhibitors confirmed PfGR but not PfoTPT as a possible factor contributing to the development of pyknosis. A reduction in total glutathione levels was also detected in association with increased pyknosis. These results further our understanding of the mechanisms responsible for P. falciparum development and the antimalarial activity of dihydroartemisinin, and provide useful information for the development of novel antimalarial agents.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0184874</identifier><identifier>PMID: 28934264</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Acids ; Antimalarial activity ; Antimalarial agents ; Antimalarials - pharmacology ; Artemisinins - pharmacology ; Benzylidene Compounds - pharmacology ; Biology and Life Sciences ; Bornanes - pharmacology ; Cannabinoid Receptor Antagonists - pharmacology ; Cannabinoid receptors ; Causes of ; Cell Death - drug effects ; Cell Death - physiology ; Chromatin - drug effects ; Chromatin - metabolism ; Comparative analysis ; Dihydroartemisinin ; Dose-Response Relationship, Drug ; Drugs ; Erythrocytes ; Gene expression ; Gene Expression Profiling ; Genetic aspects ; Genomes ; Glutathione ; Glutathione - metabolism ; Glutathione reductase ; Health aspects ; Infectious diseases ; Malaria ; Medicine ; Medicine and Health Sciences ; Membrane proteins ; Metabolism ; Naltrexone - analogs & derivatives ; Naltrexone - pharmacology ; Narcotic Antagonists - pharmacology ; Narcotics ; Opioid receptors (type delta) ; Oxidation-Reduction ; Parasites ; Parasitology ; Phosphate transporter ; Phosphates ; Physiological aspects ; Piperidines - pharmacology ; Plasmodium ; Plasmodium falciparum ; Plasmodium falciparum - drug effects ; Plasmodium falciparum - growth & development ; Plasmodium falciparum - metabolism ; Pyrazoles - pharmacology ; Transcriptome - drug effects ; Tropical diseases ; Vector-borne diseases</subject><ispartof>PloS one, 2017-09, Vol.12 (9), p.e0184874</ispartof><rights>COPYRIGHT 2017 Public Library of Science</rights><rights>2017 Asahi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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We investigated the effects of opioid and cannabinoid receptor antagonists on the growth of intraerythrocytic P. falciparum. The delta opioid receptor antagonist 7-benzylidenenaltrexone (BNTX) and the cannabinoid receptor antagonists rimonaband and SR144528 caused growth arrest of the parasite. Notably BNTX and the established antimalarial drug dihydroartemisinin induced prominent pyknosis in parasite cells after a short period of incubation. We compared genome-wide transcriptome profiles in P. falciparum with different degrees of pyknosis in response to drug treatment, and identified 11 transcripts potentially associated with the evoking of pyknosis, of which three, including glutathione reductase (PfGR), triose phosphate transporter (PfoTPT), and a conserved Plasmodium membrane protein, showed markedly different gene expression levels in accordance with the degree of pyknosis. 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We investigated the effects of opioid and cannabinoid receptor antagonists on the growth of intraerythrocytic P. falciparum. The delta opioid receptor antagonist 7-benzylidenenaltrexone (BNTX) and the cannabinoid receptor antagonists rimonaband and SR144528 caused growth arrest of the parasite. Notably BNTX and the established antimalarial drug dihydroartemisinin induced prominent pyknosis in parasite cells after a short period of incubation. We compared genome-wide transcriptome profiles in P. falciparum with different degrees of pyknosis in response to drug treatment, and identified 11 transcripts potentially associated with the evoking of pyknosis, of which three, including glutathione reductase (PfGR), triose phosphate transporter (PfoTPT), and a conserved Plasmodium membrane protein, showed markedly different gene expression levels in accordance with the degree of pyknosis. Furthermore, the use of specific inhibitors confirmed PfGR but not PfoTPT as a possible factor contributing to the development of pyknosis. A reduction in total glutathione levels was also detected in association with increased pyknosis. These results further our understanding of the mechanisms responsible for P. falciparum development and the antimalarial activity of dihydroartemisinin, and provide useful information for the development of novel antimalarial agents.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>28934264</pmid><doi>10.1371/journal.pone.0184874</doi><tpages>e0184874</tpages><orcidid>https://orcid.org/0000-0002-0127-2265</orcidid><oa>free_for_read</oa></addata></record> |
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recordid | cdi_plos_journals_1941349459 |
source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Public Library of Science (PLoS); PubMed Central; Free Full-Text Journals in Chemistry |
subjects | Acids Antimalarial activity Antimalarial agents Antimalarials - pharmacology Artemisinins - pharmacology Benzylidene Compounds - pharmacology Biology and Life Sciences Bornanes - pharmacology Cannabinoid Receptor Antagonists - pharmacology Cannabinoid receptors Causes of Cell Death - drug effects Cell Death - physiology Chromatin - drug effects Chromatin - metabolism Comparative analysis Dihydroartemisinin Dose-Response Relationship, Drug Drugs Erythrocytes Gene expression Gene Expression Profiling Genetic aspects Genomes Glutathione Glutathione - metabolism Glutathione reductase Health aspects Infectious diseases Malaria Medicine Medicine and Health Sciences Membrane proteins Metabolism Naltrexone - analogs & derivatives Naltrexone - pharmacology Narcotic Antagonists - pharmacology Narcotics Opioid receptors (type delta) Oxidation-Reduction Parasites Parasitology Phosphate transporter Phosphates Physiological aspects Piperidines - pharmacology Plasmodium Plasmodium falciparum Plasmodium falciparum - drug effects Plasmodium falciparum - growth & development Plasmodium falciparum - metabolism Pyrazoles - pharmacology Transcriptome - drug effects Tropical diseases Vector-borne diseases |
title | Profiling molecular factors associated with pyknosis and developmental arrest induced by an opioid receptor antagonist and dihydroartemisinin in Plasmodium falciparum |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-19T05%3A17%3A16IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Profiling%20molecular%20factors%20associated%20with%20pyknosis%20and%20developmental%20arrest%20induced%20by%20an%20opioid%20receptor%20antagonist%20and%20dihydroartemisinin%20in%20Plasmodium%20falciparum&rft.jtitle=PloS%20one&rft.au=Asahi,%20Hiroko&rft.date=2017-09-21&rft.volume=12&rft.issue=9&rft.spage=e0184874&rft.pages=e0184874-&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0184874&rft_dat=%3Cgale_plos_%3EA505755372%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1941349459&rft_id=info:pmid/28934264&rft_galeid=A505755372&rft_doaj_id=oai_doaj_org_article_3745decc9c0643d2bcb007f7ff7f3887&rfr_iscdi=true |