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Sent on Thursday, 2009 Aug 20Search kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"
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PubMed Results |
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Apoptosis caused by Hsp90 inhibitor geldanamycin in Leishmania donovani during promastigote-to-amastigote transformation stage.
Bio-X Center, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), College of Life Sciences and Biotechnology, Shanghai Jiao Tong University, 800 Dongchuan Road, 200240, Shanghai, China.
The role of heat shock protein 90 inhibitor geldanamycin (GA) during Leishmania donovani promastigote-to-amastigote transformation in axenic conditions was investigated. Promastigotes exhibited apoptotic morphologic changes after GA treatment at a high temperature, and the effect is in a dose- and time-dependant manner. Meanwhile, cell cycle analysis showed a significant increase at the expense of cells in the G0/G1 phase and a decrease in the S and G2/M phases after GA treatment. In addition, cellular glutathione level was reduced and reactive oxygen species content was increased afterwards. Pretreatment with antioxidants reduced the percentage of GA-induced cell apoptosis. After treatment, cultures in pH 5.5 showed a lower percentage of apoptosis than those in pH 7.4. The present study showed that GA could cause apoptosis in L. donovani but could not cause stage differentiation in high temperature and that acidic conditions were likely to be crucial for the transformation and survival of the parasite within its human host.
PMID: 19690889 [PubMed - as supplied by publisher]
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- Chronic heat-shock treatment driven differentiation induces apoptosis in Leishmania donovani.
Mol Cell Biochem. 2006 Sep; 289(1-2):83-90. Epub 2006 Jul 11.
[Mol Cell Biochem. 2006]
- Heat shock protein 90 homeostasis controls stage differentiation in Leishmania donovani.
Mol Biol Cell. 2001 Nov; 12(11):3307-16.
[Mol Biol Cell. 2001]
- Differentiation of Leishmania donovani in host-free system: analysis of signal perception and response.
Mol Biochem Parasitol. 2005 May; 141(1):99-108.
[Mol Biochem Parasitol. 2005]
- Developmentally induced changes of the proteome in the protozoan parasite Leishmania donovani.
Proteomics. 2003 Sep; 3(9):1811-29.
[Proteomics. 2003]
- ReviewThe role of pH and temperature in the development of Leishmania parasites.
Annu Rev Microbiol. 1994; 48:449-70.
[Annu Rev Microbiol. 1994]
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- Chronic heat-shock treatment driven differentiation induces apoptosis in Leishmania donovani.
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Leishmanicidal activity of new megazol derivatives.
FioCruz-Fundação Oswaldo Cruz, Instituto de Tecnologia em Fármacos - Far Manguinhos Rua Sizenando Nabuco, 100, Manguinhos, 21041-250 Rio de Janeiro, RJ, Brazil.
A series of thirteen new megazol derivatives, designed exploring the molecular hybridization approach between megazol (3) and heterocombretastatins (2), was synthesized. These new compounds were tested for in vitro antiparasitic activity upon axenic amastigotes of Leishmania donovani. Biological results led us to identify a new potent megazol derivative (4g), which presents an IC(50) = 0.081microg/mL, more active tham the reference drug miltefosine (IC(50) = 0.131microg/mL).
PMID: 19689398 [PubMed - in process]
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- Synthesis and antitrypanosomal profile of new functionalized 1,3,4-thiadiazole-2-arylhydrazone derivatives, designed as non-mutagenic megazol analogues.
Bioorg Med Chem Lett. 2004 Dec 20; 14(24):5967-70.
[Bioorg Med Chem Lett. 2004]
- Synthesis of 16-mercaptohexadecylphosphocholine, a miltefosine analog with leishmanicidal activity.
Bioorg Med Chem Lett. 2006 Oct 1; 16(19):5190-3. Epub 2006 Jul 25.
[Bioorg Med Chem Lett. 2006]
- Synthesis and biological activity of nitro heterocycles analogous to megazol, a trypanocidal lead.
J Med Chem. 2003 Jan 30; 46(3):427-40.
[J Med Chem. 2003]
- In vitro antileishmanial activity of fluoro-artemisinin derivatives against Leishmania donovani.
Biomed Pharmacother. 2008 Sep; 62(7):462-5. Epub 2008 May 15.
[Biomed Pharmacother. 2008]
- Leishmanicidal activity of edelfosine, miltefosine and ilmofosine.
Basic Clin Pharmacol Toxicol. 2005 Jan; 96(1):60-5.
[Basic Clin Pharmacol Toxicol. 2005]
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- Synthesis and antitrypanosomal profile of new functionalized 1,3,4-thiadiazole-2-arylhydrazone derivatives, designed as non-mutagenic megazol analogues.
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5-Lipoxygenase plays a role in the control of parasite burden and contributes to oxidative damage of erythrocytes in murine Chagas' disease.
Department of Pathological Sciences, Biological Sciences Center, State University of Londrina, Londrina, Paraná, Brazil.
Chagas' disease is accompanied by severe anemia and oxidative stress, which may contribute to mortality. In this study, we investigated the role of 5-lipoxygenase (5-LO) in the control of parasitism and anemia associated with oxidative damage of erythrocytes in experimental Trypanosoma cruzi infection. Wild-type C57BL/6, 129Sv mice treated or not with nordihydroguaiaretic acid (NDGA, 5-LO inhibitor), mice lacking the 5-LO enzyme gene (5-LO(-/-)) and inducible nitric oxide synthase gene (iNOS(-/-)) were infected with the Y strain of T. cruzi. Impairment of 5-LO resulted in increased numbers of trypomastigote forms in the blood and amastigote forms in the heart of infected mice. We assessed oxidative stress in erythrocytes by measuring oxygen uptake, induction time and chemiluminescence following treatment with tert-butyl hydroperoxide (TBH). Our results show that 5-LO metabolites increased lipid peroxidation levels in erythrocytes during the early phase of murine T. cruzi infection. NDGA treatment reduced oxidative damage of erythrocytes in C57BL/6 T. cruzi-infected mice but not in C57BL/6 iNOS(-/-) infected mice, showing that the action of NDGA is dependent on endogenous nitric oxide (NO). In addition, our results show that 5-LO metabolites do not participate directly in the development of anemia in infected mice. We conclude that 5-LO products may not only play a major role in controlling heart tissue parasitism, i.e., host resistance to acute infection with T. cruziin vivo, but in the event of an infection also play an important part in erythrocyte oxidative stress, an NO-dependent effect.
PMID: 19428550 [PubMed - indexed for MEDLINE]
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- Involvement of nitric oxide (NO) and TNF-alpha in the oxidative stress associated with anemia in experimental Trypanosoma cruzi infection.
FEMS Immunol Med Microbiol. 2004 May 1; 41(1):69-77.
[FEMS Immunol Med Microbiol. 2004]
- Effects of cyclooxygenase inhibitors on parasite burden, anemia and oxidative stress in murine Trypanosoma cruzi infection.
FEMS Immunol Med Microbiol. 2008 Jan; 52(1):47-58. Epub 2007 Nov 21.
[FEMS Immunol Med Microbiol. 2008]
- Pivotal role of interleukin-12 and interferon-gamma axis in controlling tissue parasitism and inflammation in the heart and central nervous system during Trypanosoma cruzi infection.
Am J Pathol. 2001 Nov; 159(5):1723-33.
[Am J Pathol. 2001]
- Protective immunity against Trypanosoma cruzi provided by oral immunization with Phytomonas serpens: role of nitric oxide.
Immunol Lett. 2005 Jan 31; 96(2):283-90.
[Immunol Lett. 2005]
- ReviewImmunological control of Trypanosoma cruzi infection and pathogenesis of Chagas' disease.
Int Arch Allergy Immunol. 1997 Oct; 114(2):103-10.
[Int Arch Allergy Immunol. 1997]
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- Involvement of nitric oxide (NO) and TNF-alpha in the oxidative stress associated with anemia in experimental Trypanosoma cruzi infection.
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Genotyping of Panamanian Trypanosoma cruzi stocks using the calmodulin 3'UTR polymorphisms.
Oswaldo Cruz Institute, Fiocruz, Rio de Janiero, Brazil.
Mutations in the 3' untranslated region of calmodulin gene have recently been reported to be specific to different Trypanosoma cruzi lineages. In the present report, this molecular marker was used to genotype 24 T. cruzi isolates from humans and vectors from different endemic areas in Panama. The finding of solely T. cruzi I genotype might explain the low morbidity of Chagas' disease in the region when compared to other countries in Latin America.
PMID: 18165887 [PubMed - indexed for MEDLINE]
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- Trypanosoma cruzi: Mutations in the 3' untranslated region of calmodulin gene are specific for lineages T. cruzi I, T. cruzi II, and the Zymodeme III isolates.
Exp Parasitol. 2006 Apr; 112(4):247-52. Epub 2005 Dec 20.
[Exp Parasitol. 2006]
- Probing population dynamics of Trypanosoma cruzi during progression of the chronic phase in chagasic patients.
J Clin Microbiol. 2009 Jun; 47(6):1718-25. Epub 2009 Apr 8.
[J Clin Microbiol. 2009]
- AU-rich elements in the 3'-untranslated region of a new mucin-type gene family of Trypanosoma cruzi confers mRNA instability and modulates translation efficiency.
J Biol Chem. 2000 Apr 7; 275(14):10218-27.
[J Biol Chem. 2000]
- Molecular characterization of human Trypanosoma cruzi isolates from endemic areas in Panama.
Mem Inst Oswaldo Cruz. 2006 Jun; 101(4):455-7.
[Mem Inst Oswaldo Cruz. 2006]
- ReviewTriatominae-Trypanosoma cruzi/T. rangeli: Vector-parasite interactions.
Acta Trop. 2009 May-Jun; 110(2-3):137-47. Epub 2008 Oct 15.
[Acta Trop. 2009]
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- Trypanosoma cruzi: Mutations in the 3' untranslated region of calmodulin gene are specific for lineages T. cruzi I, T. cruzi II, and the Zymodeme III isolates.
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