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Downregulation of Calcineurin Gene Is Associated with Glucantime(®) Resiatance in Leishmania infantum

BACKGROUND: Pentavalent antimonials are the first line drugs for the treatment of leishmaniasis. Unresponsiveness of Leishmania spp. to antimonial drugs is a serious problem in some endemic areas. Investigations on molecular mechanisms involved in drug resistance are essential for monitoring and man...

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Autores principales: Bagher KHADEM ERFAN, Mohammad, MOHEBALI, Mehdi, KAZEMI-RAD, Elham, HAJJARAN, Homa, EDRISSIAN, GholamHossein, MAMISHI, Setareh, SAFFARi, Mojtaba, RAOOFIAN, Reza, HEIDARI, Mansour
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Tehran University of Medical Sciences 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3887235/
https://www.ncbi.nlm.nih.gov/pubmed/24454427
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author Bagher KHADEM ERFAN, Mohammad
MOHEBALI, Mehdi
KAZEMI-RAD, Elham
HAJJARAN, Homa
EDRISSIAN, GholamHossein
MAMISHI, Setareh
SAFFARi, Mojtaba
RAOOFIAN, Reza
HEIDARI, Mansour
author_facet Bagher KHADEM ERFAN, Mohammad
MOHEBALI, Mehdi
KAZEMI-RAD, Elham
HAJJARAN, Homa
EDRISSIAN, GholamHossein
MAMISHI, Setareh
SAFFARi, Mojtaba
RAOOFIAN, Reza
HEIDARI, Mansour
author_sort Bagher KHADEM ERFAN, Mohammad
collection PubMed
description BACKGROUND: Pentavalent antimonials are the first line drugs for the treatment of leishmaniasis. Unresponsiveness of Leishmania spp. to antimonial drugs is a serious problem in some endemic areas. Investigations on molecular mechanisms involved in drug resistance are essential for monitoring and managing of the disease. Cal-cineurin is an essential protein phosphatase for number of signal transduction pathways in eukaryotic cells and it has a mediated role in apoptosis. This study aimed to determine of biomarker(s) in Glucantime(®) resiatance strain of L. infan-tum. METHODS: We used cDNA amplified fragment length polymorphism (cDNA-AFLP) and real time-RT PCR assays to compare gene expression profiles at the mRNA levels in resistant and susceptible L. infantum field isolates. RESULTS: The cDNA-AFLP results showed downlegulation of calcineurin in resis-tant isolate in comparison with susceptible one. Significant downregulation of cal-cineurin (0.42 fold) (P<0.05) was found in resistant isolate compared to susceptible one by Real time-RT PCR. CONCLUSION: This is the first report of calcineurin implication in Glucantime(®) drug resistance of field (natural) isolate of L. infantum. Downregulation of calcineurin could protect parasites from antimonial-induced apoptosis.
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spelling pubmed-38872352014-01-21 Downregulation of Calcineurin Gene Is Associated with Glucantime(®) Resiatance in Leishmania infantum Bagher KHADEM ERFAN, Mohammad MOHEBALI, Mehdi KAZEMI-RAD, Elham HAJJARAN, Homa EDRISSIAN, GholamHossein MAMISHI, Setareh SAFFARi, Mojtaba RAOOFIAN, Reza HEIDARI, Mansour Iran J Parasitol Original Article BACKGROUND: Pentavalent antimonials are the first line drugs for the treatment of leishmaniasis. Unresponsiveness of Leishmania spp. to antimonial drugs is a serious problem in some endemic areas. Investigations on molecular mechanisms involved in drug resistance are essential for monitoring and managing of the disease. Cal-cineurin is an essential protein phosphatase for number of signal transduction pathways in eukaryotic cells and it has a mediated role in apoptosis. This study aimed to determine of biomarker(s) in Glucantime(®) resiatance strain of L. infan-tum. METHODS: We used cDNA amplified fragment length polymorphism (cDNA-AFLP) and real time-RT PCR assays to compare gene expression profiles at the mRNA levels in resistant and susceptible L. infantum field isolates. RESULTS: The cDNA-AFLP results showed downlegulation of calcineurin in resis-tant isolate in comparison with susceptible one. Significant downregulation of cal-cineurin (0.42 fold) (P<0.05) was found in resistant isolate compared to susceptible one by Real time-RT PCR. CONCLUSION: This is the first report of calcineurin implication in Glucantime(®) drug resistance of field (natural) isolate of L. infantum. Downregulation of calcineurin could protect parasites from antimonial-induced apoptosis. Tehran University of Medical Sciences 2013 /pmc/articles/PMC3887235/ /pubmed/24454427 Text en © 2013 Iranian Society of Parasitology & Tehran University of Medical Sciences http://creativecommons.org/licenses/by/2.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Article
Bagher KHADEM ERFAN, Mohammad
MOHEBALI, Mehdi
KAZEMI-RAD, Elham
HAJJARAN, Homa
EDRISSIAN, GholamHossein
MAMISHI, Setareh
SAFFARi, Mojtaba
RAOOFIAN, Reza
HEIDARI, Mansour
Downregulation of Calcineurin Gene Is Associated with Glucantime(®) Resiatance in Leishmania infantum
title Downregulation of Calcineurin Gene Is Associated with Glucantime(®) Resiatance in Leishmania infantum
title_full Downregulation of Calcineurin Gene Is Associated with Glucantime(®) Resiatance in Leishmania infantum
title_fullStr Downregulation of Calcineurin Gene Is Associated with Glucantime(®) Resiatance in Leishmania infantum
title_full_unstemmed Downregulation of Calcineurin Gene Is Associated with Glucantime(®) Resiatance in Leishmania infantum
title_short Downregulation of Calcineurin Gene Is Associated with Glucantime(®) Resiatance in Leishmania infantum
title_sort downregulation of calcineurin gene is associated with glucantime(®) resiatance in leishmania infantum
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3887235/
https://www.ncbi.nlm.nih.gov/pubmed/24454427
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