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

  • Mohammad Bagher Khadem Erfan Department of Medical Parasitology and Mycology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
  • Mehdi Mohebali Department of Medical Parasitology and Mycology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran AND Center for Research of Endemic Parasites of Iran (CREPI), Tehran University of Medical Sciences, Tehran, Iran.
  • Elham Kazemi-Rad Department of Medical Parasitology and Mycology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
  • Homa Hajjaran Department of Medical Parasitology and Mycology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
  • Gholamhossein Edrissian Department of Medical Parasitology and Mycology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
  • Setareh Mamishi Pediatric Infectious Diseases Research Center, Tehran University of Medical Sciences, Tehran, Iran.
  • Mojtaba Saffari Department of Medical Genetics, Tehran University of Medical Sciences, Tehran, Iran.
  • Reza Raoofian Department of Medical Genetics, Tehran University of Medical Sciences, Tehran, Iran.
  • Mansour Heidari Department of Medical Genetics, Tehran University of Medical Sciences, Tehran, Iran AND Stem Cell Preparation Unit, Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, Iran.
Keywords: Antimonial resistance, Calcineurin gene, Leishmania infantum, Real-time RT-PCR, cDNA-AFLP

Abstract

 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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How to Cite
1.
Bagher Khadem Erfan M, Mohebali M, Kazemi-Rad E, Hajjaran H, Edrissian G, Mamishi S, Saffari M, Raoofian R, Heidari M. Downregulation of Calcineurin Gene Is Associated with Glucantime(®) Resiatance in Leishmania infantum. IJPA. 8(3):359-66.
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