The Calpain Inhibitor MDL28170 Induces the Expression of Apoptotic Markers in Leishmania amazonensis Promastigotes
| العنوان: | The Calpain Inhibitor MDL28170 Induces the Expression of Apoptotic Markers in Leishmania amazonensis Promastigotes |
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| المؤلفون: | Claudia M. d’Avila-Levy, Simone S.C. Oliveira, Maria Bellio, Diego de Souza Gonçalves, Filipe P. Matteoli, Keyla C. S. Gonçalves, Thaïs Souto-Padrón, Marta H. Branquinha, André L.S. Santos, Ana Carolina Oliveira, Sergio H. Seabra, Fernanda A. Marinho, Selma Soares de Oliveira |
| المصدر: | PLoS ONE PLoS ONE, Vol 9, Iss 1, p e87659 (2014) |
| بيانات النشر: | Public Library of Science, 2014. |
| سنة النشر: | 2014 |
| مصطلحات موضوعية: | Protozoan Proteins, lcsh:Medicine, Apoptosis, Protozoology, chemistry.chemical_compound, Molecular Cell Biology, Signaling in Cellular Processes, lcsh:Science, Leishmaniasis, Apoptotic Signaling, Leishmania, Membrane Potential, Mitochondrial, Multidisciplinary, TUNEL assay, biology, Calpain, Dipeptides, Infectious Diseases, DNA fragmentation, Medicine, Research Article, Signal Transduction, Neglected Tropical Diseases, Leishmaniasis, Cutaneous, DNA Fragmentation, Cysteine Proteinase Inhibitors, Microbiology, Resting Phase, Cell Cycle, Cutaneous leishmaniasis, medicine, Parasitic Diseases, Humans, Propidium iodide, Fragmentation (cell biology), Biology, lcsh:R, Parasite Physiology, G1 Phase, DNA, Protozoan, biology.organism_classification, medicine.disease, Molecular biology, chemistry, Gene Expression Regulation, biology.protein, Parastic Protozoans, lcsh:Q, Parasitology |
| الوصف: | Background Human cutaneous leishmaniasis is caused by distinct species, including Leishmania amazonensis. Treatment of cutaneous leishmaniasis is far from satisfactory due to increases in drug resistance and relapses, and toxicity of compounds to the host. As a consequence for this situation, the development of new leishmanicidal drugs and the search of new targets in the parasite biology are important goals. Methodology/Principal Findings In this study, we investigated the mechanism of death pathway induced by the calpain inhibitor MDL28170 on Leishmania amazonensis promastigote forms. The combined use of different techniques was applied to contemplate this goal. MDL28170 treatment with IC50 (15 µM) and two times the IC50 doses induced loss of parasite viability, as verified by resazurin assay, as well as depolarization of the mitochondrial membrane, which was quantified by JC-1 staining. Scanning and transmission electron microscopic images revealed drastic alterations on the parasite morphology, some of them resembling apoptotic-like death, including cell shrinking, surface membrane blebs and altered chromatin condensation pattern. The lipid rearrangement of the plasma membrane was detected by Annexin-V labeling. The inhibitor also induced a significant increase in the proportion of cells in the sub-G0/G1 phase, as quantified by propidium iodide staining, as well as genomic DNA fragmentation, detected by TUNEL assay. In cells treated with MDL28170 at two times the IC50 dose, it was also possible to observe an oligonucleossomal DNA fragmentation by agarose gel electrophoresis. Conclusions/Significance The data presented in the current study suggest that MDL28170 induces apoptotic marker expression in promastigotes of L. amazonensis. Altogether, the results described in the present work not only provide a rationale for further exploration of the mechanism of action of calpain inhibitors against trypanosomatids, but may also widen the investigation of the potential clinical utility of calpain inhibitors in the chemotherapy of leishmaniases. |
| اللغة: | English |
| تدمد: | 1932-6203 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e7e7bf9c7f13929205a36956d4d5bec5Test http://europepmc.org/articles/PMC3909198Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....e7e7bf9c7f13929205a36956d4d5bec5 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19326203 |
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