Abstract:
:Procyclic Trypanosoma brucei brucei strain 366D is susceptible to DL-alpha-difluoromethylornithine (DFMO) with an in vitro ED50 value of 225 microM. A mutant of the procyclic strain resistant to 20 mM of DFMO was isolated by serial in vitro passages of the organisms in increasing concentrations of the drug. Drug resistance remains unchanged after at least ten serial passages in the absence of DFMO. The mutant contains the same level of ornithine decarboxylase activity as the wild-type procyclic, and the mutant enzyme exhibits a similar susceptibility toward DFMO as the wild type. Neither the rate of decarboxylation of ornithine, nor the membrane potential in the mutant cell is changed. The only observed change in the mutant is its significantly decreased uptake of DFMO which reaches a saturating level of 18 microM inside the cells; a concentration seven times below the Ki value of DFMO on T. brucei ornithine decarboxylase (130 microM). Apparently, the failure of DFMO uptake in the mutant strain has provided the basis of drug resistance. The results also raise the question on whether the uptake of DFMO by T. brucei is by passive diffusion or by transporter(s) mediation. DFMO does not compete with the uptake of ornithine, arginine or putrescine, and the reverse holds also true. However, the mutant strain cultivated under DFMO for several generations has a greatly enhanced uptake of ornithine and a moderately heightened uptake of putrescine. Both are reduced to the normal level upon further propagations of the mutant strain in the absence of DFMO.
journal_name
Mol Biochem Parasitoljournal_title
Molecular and biochemical parasitologyauthors
Phillips MA,Wang CCdoi
10.1016/0166-6851(87)90064-8subject
Has Abstractpub_date
1987-01-02 00:00:00pages
9-17issue
1eissn
0166-6851issn
1872-9428pii
0166-6851(87)90064-8journal_volume
22pub_type
杂志文章abstract::Peptidomimetic inhibitors of mammalian zinc metalloproteases have been tested as potential agents for intervention in disease caused by kinetoplastid protozoa. Certain metalloprotease inhibitors were able to inhibit the release of variant surface glycoprotein from cultured transgenic procyclic Trypanosoma brucei, conf...
journal_title:Molecular and biochemical parasitology
pub_type: 杂志文章
doi:10.1016/s0166-6851(01)00244-4
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abstract::Plasmodium falciparum trophozoites were isolated by mechanical rupture of infected human erythrocytes followed by a series of differential centrifugation steps. After lysis with sonication, the 100 000 x g supernatant of parasites and uninfected host cells was used to determine the specific activities of a number of e...
journal_title:Molecular and biochemical parasitology
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doi:10.1016/0166-6851(82)90035-4
更新日期:1982-05-01 00:00:00
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journal_title:Molecular and biochemical parasitology
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更新日期:2007-06-01 00:00:00
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journal_title:Molecular and biochemical parasitology
pub_type: 杂志文章
doi:10.1016/j.molbiopara.2004.05.008
更新日期:2004-09-01 00:00:00
abstract::The membrane potential and pH gradient over the plasma membrane of the protozoan parasite Trypanosoma brucei were measured with radioactive indicators in combination with the silicone oil centrifugation technique over a range of temperatures. At 37 degrees C a small membrane potential and pH gradient of similar magnit...
journal_title:Molecular and biochemical parasitology
pub_type: 杂志文章
doi:10.1016/0166-6851(92)90123-2
更新日期:1992-10-01 00:00:00
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journal_title:Molecular and biochemical parasitology
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doi:10.1016/j.molbiopara.2007.06.002
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journal_title:Molecular and biochemical parasitology
pub_type: 杂志文章
doi:10.1016/j.molbiopara.2005.02.010
更新日期:2005-06-01 00:00:00
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journal_title:Molecular and biochemical parasitology
pub_type: 杂志文章
doi:10.1016/0166-6851(84)90084-7
更新日期:1984-07-01 00:00:00
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更新日期:2002-09-01 00:00:00
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pub_type: 杂志文章
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更新日期:2002-03-01 00:00:00
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更新日期:2017-09-01 00:00:00
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journal_title:Molecular and biochemical parasitology
pub_type: 杂志文章
doi:10.1016/0166-6851(80)90050-x
更新日期:1980-10-01 00:00:00
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journal_title:Molecular and biochemical parasitology
pub_type: 杂志文章
doi:10.1016/j.molbiopara.2012.09.009
更新日期:2012-11-01 00:00:00
abstract::Adult males and females of the dog heartworm, Dirofilaria immitis, were extracted separately and, following separation of the free and conjugated ecdysteroid fractions, the conjugates were hydrolysed enzymically. Both the ecdysteroids released by hydrolysis of the conjugates and the free hormones were further purified...
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pub_type: 杂志文章
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更新日期:1983-11-01 00:00:00
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journal_title:Molecular and biochemical parasitology
pub_type: 杂志文章
doi:10.1016/0166-6851(92)90022-c
更新日期:1992-07-01 00:00:00
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journal_title:Molecular and biochemical parasitology
pub_type: 杂志文章
doi:10.1016/s0166-6851(03)00055-0
更新日期:2003-05-01 00:00:00
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pub_type: 杂志文章
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更新日期:2014-03-01 00:00:00
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journal_title:Molecular and biochemical parasitology
pub_type: 杂志文章,评审
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更新日期:2001-07-01 00:00:00
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更新日期:2016-08-01 00:00:00
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journal_title:Molecular and biochemical parasitology
pub_type: 杂志文章
doi:10.1016/0166-6851(85)90029-5
更新日期:1985-04-01 00:00:00
abstract::Plasmodium falciparum is the causative organism for the most severe form of malaria among humans. The clinical symptoms are accredited to the asexual stage of parasite life cycle, involving merozoite invasion of erythrocyte, development and re-invasion into the new erythrocyte. Interaction of parasite proteins present...
journal_title:Molecular and biochemical parasitology
pub_type: 杂志文章
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更新日期:2015-08-01 00:00:00
abstract::Given the growing appreciation of serious health sequelae from widespread Trichomonas vaginalis infection, new tools are needed to study the parasite's genetic diversity. To this end we have identified and characterized a panel of 21 microsatellites and six single-copy genes from the T. vaginalis genome, using seven l...
journal_title:Molecular and biochemical parasitology
pub_type: 杂志文章
doi:10.1016/j.molbiopara.2010.08.006
更新日期:2011-01-01 00:00:00
abstract::In Leishmania mexicana two genes were detected coding for different isoforms of the glycolytic enzyme phosphoglycerate kinase. This situation contrasts with that observed in other Trypanosomatidae (Trypanosoma brucei, Trypanosoma congolense, Crithidia fasciculata) analyzed previously, which all contain three different...
journal_title:Molecular and biochemical parasitology
pub_type: 杂志文章
doi:10.1016/s0166-6851(97)00152-7
更新日期:1997-12-01 00:00:00
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journal_title:Molecular and biochemical parasitology
pub_type: 杂志文章
doi:10.1016/j.molbiopara.2010.05.006
更新日期:2010-10-01 00:00:00
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journal_title:Molecular and biochemical parasitology
pub_type: 杂志文章
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更新日期:2017-12-01 00:00:00
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journal_title:Molecular and biochemical parasitology
pub_type: 杂志文章
doi:10.1016/0166-6851(92)90240-k
更新日期:1992-01-01 00:00:00
abstract::Electron paramagnetic resonance spectrometry (EPR) techniques revealed a complex set of redox components in intact respiring cells of Tritrichomonas foetus, an aerotolerant anaerobic protozoon which lacks mitochondria. One of the two main systems of terminal respiration of this organism is the hydrogenosomal system, w...
journal_title:Molecular and biochemical parasitology
pub_type: 杂志文章
doi:10.1016/0166-6851(80)90047-x
更新日期:1980-10-01 00:00:00
abstract::The separation by chromatofocusing of two distinct purine nucleoside cleaving activities from crude extracts of Trypanosoma brucei brucei is described. One catalyzes the reversible phosphorolysis of 5'-deoxy-5'-methylthioadenosine (MeSAdo) and adenosine (Ado) and was designated an MeSAdo/Ado phosphorylase, while the o...
journal_title:Molecular and biochemical parasitology
pub_type: 杂志文章
doi:10.1016/0166-6851(88)90030-8
更新日期:1988-01-15 00:00:00