| Proteasome inhibitors block development of Plasmodium spp. | |
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MedLine Citation:
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PMID: 9756786 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Proteasomes degrade most of the proteins inside eukaryotic cells, including transcription factors and regulators of cell cycle progression. Here we show that nanomolar concentrations of lactacystin, a specific irreversible inhibitor of the 20S proteasome, inhibit development of the exoerythrocytic and erythrocytic stages of the malaria parasite. Although lactacystin-treated Plasmodium berghei sporozoites are still invasive, their development into exoerythrocytic forms (EEF) is inhibited in vitro and in vivo. Erythrocytic schizogony of P. falciparum in vitro is also profoundly inhibited when drug treatment of the synchronized parasites is prior, but not subsequent, to the initiation of DNA synthesis, suggesting that the inhibitory effect of lactacystin is cell cycle specific. Lactacystin reduces P. berghei parasitemia in rats, but the therapeutic index is very low. Along with other studies showing that lactacystin inhibits stage-specific transformation in Trypanosoma and Entamoeba spp., these findings highlight the potential of proteasome inhibitors as drugs for the treatment of diseases caused by protozoan parasites. |
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Authors:
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S M Gantt; J M Myung; M R Briones; W D Li; E J Corey; S Omura; V Nussenzweig; P Sinnis |
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Publication Detail:
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Type: Journal Article; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Antimicrobial agents and chemotherapy Volume: 42 ISSN: 0066-4804 ISO Abbreviation: Antimicrob. Agents Chemother. Publication Date: 1998 Oct |
Date Detail:
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Created Date: 1998-11-09 Completed Date: 1998-11-09 Revised Date: 2011-01-13 |
Medline Journal Info:
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Nlm Unique ID: 0315061 Medline TA: Antimicrob Agents Chemother Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 2731-8 Citation Subset: IM |
Affiliation:
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Department of Pathology, NYU Medical Center, New York, New York 10016, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Acetylcysteine
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analogs & derivatives,
pharmacology Animals Antimalarials / pharmacology* Cysteine Endopeptidases / drug effects* Cysteine Proteinase Inhibitors / pharmacology* Erythrocytes / parasitology Humans Hypoxanthine / metabolism Multienzyme Complexes / drug effects* Plasmodium / drug effects*, growth & development Proteasome Endopeptidase Complex Rats Rats, Sprague-Dawley |
| Grant Support | |
ID/Acronym/Agency:
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K11 AI001175-05/AI/NIAID NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antimalarials; 0/Cysteine Proteinase Inhibitors; 0/Multienzyme Complexes; 133343-34-7/lactacystin; 616-91-1/Acetylcysteine; 68-94-0/Hypoxanthine; EC 3.4.22.-/Cysteine Endopeptidases; EC 3.4.25.1/Proteasome Endopeptidase Complex |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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