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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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Detalles Bibliográficos
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
Descripción
Sumario: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.