Proteomic analysis of Plasmodium falciparum response to isocryptolepine derivative
Identifieur interne : 000508 ( Main/Exploration ); précédent : 000507; suivant : 000509Proteomic analysis of Plasmodium falciparum response to isocryptolepine derivative
Auteurs : Kitiya Rujimongkon [Thaïlande] ; Mathirut Mungthin [Thaïlande] ; Jumreang Tummatorn [Thaïlande] ; Sumate Ampawong [Thaïlande] ; Poom Adisakwattana [Thaïlande] ; Usa Boonyuen [Thaïlande] ; Onrapak Reamtong [Thaïlande]Source :
- PLoS ONE [ 1932-6203 ] ; 2019.
Abstract
Drug-resistant strains of malaria parasites have emerged for most of antimalarial medications. A new chemotherapeutic compound is needed for malarial therapy. Antimalarial activity against both drug-sensitive and drug-resistant
Url:
DOI: 10.1371/journal.pone.0220871
PubMed: 31393938
PubMed Central: 6687117
Affiliations:
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type="main">Proteomic analysis of <italic>Plasmodium falciparum</italic> response to isocryptolepine derivative</title><author><name sortKey="Rujimongkon, Kitiya" sort="Rujimongkon, Kitiya" uniqKey="Rujimongkon K" first="Kitiya" last="Rujimongkon">Kitiya Rujimongkon</name><affiliation wicri:level="1"><nlm:aff id="aff001"><addr-line>Department of Molecular Tropical Medicine and Genetics, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand</addr-line></nlm:aff><country xml:lang="fr">Thaïlande</country><wicri:regionArea>Department of Molecular Tropical Medicine and Genetics, Faculty of Tropical Medicine, Mahidol University, Bangkok</wicri:regionArea><wicri:noRegion>Bangkok</wicri:noRegion></affiliation></author><author><name sortKey="Mungthin, Mathirut" sort="Mungthin, Mathirut" uniqKey="Mungthin M" first="Mathirut" last="Mungthin">Mathirut Mungthin</name><affiliation wicri:level="1"><nlm:aff id="aff002"><addr-line>Department of Pharmacology, Phramongkutklao College of Medicine, Bangkok, Thailand</addr-line></nlm:aff><country xml:lang="fr">Thaïlande</country><wicri:regionArea>Department of Pharmacology, Phramongkutklao College of Medicine, Bangkok</wicri:regionArea><wicri:noRegion>Bangkok</wicri:noRegion></affiliation></author><author><name sortKey="Tummatorn, Jumreang" sort="Tummatorn, Jumreang" uniqKey="Tummatorn J" first="Jumreang" last="Tummatorn">Jumreang Tummatorn</name><affiliation wicri:level="1"><nlm:aff id="aff003"><addr-line>Program on Chemical Biology, Chulabhorn Graduate Institute, Center of Excellence on Environmental Health and Toxicology, Ministry of Education, Bangkok, Thailand</addr-line></nlm:aff><country xml:lang="fr">Thaïlande</country><wicri:regionArea>Program on Chemical Biology, Chulabhorn Graduate Institute, Center of Excellence on Environmental Health and Toxicology, Ministry of Education, Bangkok</wicri:regionArea><wicri:noRegion>Bangkok</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff004"><addr-line>Laboratory of Medicinal Chemistry, Chulabhorn Research Institute, Bangkok, Thailand</addr-line></nlm:aff><country xml:lang="fr">Thaïlande</country><wicri:regionArea>Laboratory of Medicinal Chemistry, Chulabhorn Research Institute, Bangkok</wicri:regionArea><wicri:noRegion>Bangkok</wicri:noRegion></affiliation></author><author><name sortKey="Ampawong, Sumate" sort="Ampawong, Sumate" uniqKey="Ampawong S" first="Sumate" last="Ampawong">Sumate Ampawong</name><affiliation wicri:level="1"><nlm:aff id="aff005"><addr-line>Department of Tropical Pathology, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand</addr-line></nlm:aff><country xml:lang="fr">Thaïlande</country><wicri:regionArea>Department of Tropical Pathology, Faculty of Tropical Medicine, Mahidol University, Bangkok</wicri:regionArea><wicri:noRegion>Bangkok</wicri:noRegion></affiliation></author><author><name sortKey="Adisakwattana, Poom" sort="Adisakwattana, Poom" uniqKey="Adisakwattana P" first="Poom" last="Adisakwattana">Poom Adisakwattana</name><affiliation wicri:level="1"><nlm:aff id="aff006"><addr-line>Department of Helminthology, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand</addr-line></nlm:aff><country xml:lang="fr">Thaïlande</country><wicri:regionArea>Department of Helminthology, Faculty of Tropical Medicine, Mahidol University, Bangkok</wicri:regionArea><wicri:noRegion>Bangkok</wicri:noRegion></affiliation></author><author><name sortKey="Boonyuen, Usa" sort="Boonyuen, Usa" uniqKey="Boonyuen U" first="Usa" last="Boonyuen">Usa Boonyuen</name><affiliation wicri:level="1"><nlm:aff id="aff001"><addr-line>Department of Molecular Tropical Medicine and Genetics, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand</addr-line></nlm:aff><country xml:lang="fr">Thaïlande</country><wicri:regionArea>Department of Molecular Tropical Medicine and Genetics, Faculty of Tropical Medicine, Mahidol University, Bangkok</wicri:regionArea><wicri:noRegion>Bangkok</wicri:noRegion></affiliation></author><author><name sortKey="Reamtong, Onrapak" sort="Reamtong, Onrapak" uniqKey="Reamtong O" first="Onrapak" last="Reamtong">Onrapak Reamtong</name><affiliation wicri:level="1"><nlm:aff id="aff001"><addr-line>Department of Molecular Tropical Medicine and Genetics, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand</addr-line></nlm:aff><country xml:lang="fr">Thaïlande</country><wicri:regionArea>Department of Molecular Tropical Medicine and Genetics, Faculty of Tropical Medicine, Mahidol University, Bangkok</wicri:regionArea><wicri:noRegion>Bangkok</wicri:noRegion></affiliation></author></analytic><series><title level="j">PLoS ONE</title><idno type="eISSN">1932-6203</idno><imprint><date when="2019">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Drug-resistant strains of malaria parasites have emerged for most of antimalarial medications. A new chemotherapeutic compound is needed for malarial therapy. Antimalarial activity against both drug-sensitive and drug-resistant <italic>P</italic>. <italic>falciparum</italic> has been reported for an isocryptolepine derivative, 8-bromo-2-fluoro-5-methyl-5H-indolo[3,2-c]quinoline (ICL-M), which also showed less toxicity to human cells. ICL-M has indoloquinoline as a core structure and its mode of action remains unclear. Here, we explored the mechanisms of ICL-M in <italic>P</italic>. <italic>falciparum</italic> by assessing the stage-specific activity, time-dependent effect, a proteomic analysis and morphology. Since human topo II activity inhibition has been reported as a function of isocryptolepine derivatives, malarial topo II activity inhibition of ICL-M was also examined in this study. The ICL-M exhibited antimalarial activity against both the ring and trophozoite stages of <italic>P</italic>. <italic>falciparum</italic>. Our proteomics analysis revealed that a total of 112 <italic>P</italic>. <italic>falciparum</italic> proteins were differentially expressed after ICL-M exposure; among these, 58 and 54 proteins were upregulated and downregulated, respectively. Proteins localized in the food vacuole, nucleus, and cytoplasm showed quantitative alterations after ICL-M treatment. A bioinformatic analysis revealed that pathways associated with ribosomes, proteasomes, metabolic pathways, amino acid biosynthesis, oxidative phosphorylation, and carbon metabolism were significantly different in <italic>P</italic>. <italic>falciparum</italic> treated with ICL-M. Moreover, a loss of ribosomes was clearly observed by transmission electron microscopy in the ICL-M-treated <italic>P</italic>. <italic>falciparum</italic>. This finding is in agreement with the proteomics data, which revealed downregulated levels of ribosomal proteins following ICL-M treatment. Our results provide important information about the mechanisms by which ICL-M affects the malaria parasite, which may facilitate the drug development of isocryptolepine derivatives.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Willcox, Ml" uniqKey="Willcox M">ML Willcox</name></author><author><name sortKey="Bodeker, G" uniqKey="Bodeker G">G Bodeker</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Grellier, P" uniqKey="Grellier P">P Grellier</name></author><author><name sortKey="Ramiaramanana, L" uniqKey="Ramiaramanana L">L Ramiaramanana</name></author><author><name sortKey="Millerioux, V" uniqKey="Millerioux V">V Millerioux</name></author><author><name sortKey="Deharo, E" uniqKey="Deharo E">E Deharo</name></author><author><name sortKey="Schrevel, J" uniqKey="Schrevel J">J Schrével</name></author><author><name sortKey="Frappier, F" uniqKey="Frappier F">F 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last="Mungthin">Mathirut Mungthin</name><name sortKey="Reamtong, Onrapak" sort="Reamtong, Onrapak" uniqKey="Reamtong O" first="Onrapak" last="Reamtong">Onrapak Reamtong</name><name sortKey="Tummatorn, Jumreang" sort="Tummatorn, Jumreang" uniqKey="Tummatorn J" first="Jumreang" last="Tummatorn">Jumreang Tummatorn</name><name sortKey="Tummatorn, Jumreang" sort="Tummatorn, Jumreang" uniqKey="Tummatorn J" first="Jumreang" last="Tummatorn">Jumreang Tummatorn</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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