Journal Information
Vol. 15. Issue 5.
Pages 442-448 (September - October 2011)
Share
Share
Download PDF
More article options
Vol. 15. Issue 5.
Pages 442-448 (September - October 2011)
Original article
Open Access
Miltefosine induces metacaspase and PARP genes expression in Leishmania infantum
Visits
2798
Shahram Khademvatan1,2, Mohammad Javad Gharavi3, Jasem Saki1,4,
Corresponding author
jasem.saki@gmail.com

Correspondence to: Department of Medical Parasitology Jundishapur University of Medical Sciences Ahvaz, Iran PO Box: 613715794 Phone: (+98 611) 3367543-50 Fax: (+98 611) 333203.
1 Department of Medical Parasitology, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
2 Infectious and Tropical Disease Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
3 Department of Medical Parasitology and Mycology, Faculty of Allied Medicine, Tehran University of Medical Sciences, Tehran, Iran
4 Cellular and Molecular Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
This item has received

Under a Creative Commons license
Article information
Abstract
Bibliography
Download PDF
Statistics
Abstract
Objectives

Apoptosis is the process of programmed cell death (PCD) that occurs in both animal and plant cells. Protozoan parasites possess metacaspase and these caspase-related proteases could be involved in the PCD pathways in these organisms. Therefore we analyzed the activities of metacaspase and PARP genes in Leishmania infantum (MCAN/IR/96/LON49) treated with miltefosine.

Materials and Methods

Anti-leishmania activity of miltefosine was studied by treatment of cultured promastigotes with various concentration of miltefosine. MTT assay and Annexin-V FLUOS staining by using FACS flow cytometry methods were used. Cytotoxic potential of HePC on the amastigots of L. infantum was evaluated in J774 cell line. In addition, metacaspase and PARP genes expression of treated L. infantum were studied.

Results

Miltefosine led to dose-dependent death of L. infantum with features compatible with apoptosis. Over expression of metacaspase and PARP was seen 6 hr after treatment.

Conclusions

Our study showed that miltefosine exerts cytotoxic effect on L. infantum via an apoptotic-related mechanism.

Keywords:
Leishmania infantum
apoptosis
gene expression
Full text is only aviable in PDF
References
[1.]
T.J. Reape, P.F. McCabe.
Apoptotic-like regulation of programmed cell death in plants.
Apoptosis, 15 (2010), pp. 249-256
[2.]
J. Kaur, N. Singh, B.K. Singh, et al.
Leishmania donovani: oral therapy with glycosyl 1,4-dihydropyridine analogue showing apoptosis like phenotypes targeting pteridine reductase 1 in intracellular amastigotes.
Exp Parasitol, 125 (2010), pp. 310-314
[3.]
J.R. Luque-Ortega, L. Rivas.
Characterization of the leishmanicidal activity of antimicrobial peptides.
Methods Mol Biol, 618 (2010), pp. 393-420
[4.]
P. Mukherjee, S.B. Majee, S. Ghosh, et al.
Apoptosis-like death in Leishmania donovani promastigotes induced by diospyrin and its ethanolamine derivative.
Int J Antimicrob Agents, 34 (2009), pp. 596-601
[5.]
M.M. Kulkarni, W.R. McMaster, W. Kamysz, et al.
Antimicrobial peptide-induced apoptotic death of leishmania results from calcium-dependent, caspase-independent mitochondrial toxicity.
J Biol Chem, 284 (2009), pp. 15496-15504
[6.]
H. Zangger, J.C. Mottram, N. Fasel.
Cell death in Leishmania induced by stress and differentiation: programmed cell death or necrosis?.
Cell Death Differ, 9 (2002), pp. 1126-1139
[7.]
A. Bera, S. Singh, R. Nagaraj, et al.
Induction of autophagic cell death in Leishmania donovani by antimicrobial peptides.
Mol Biochem Parasitol, 127 (2003), pp. 23-35
[8.]
S. Elmore.
Apoptosis: a review of programmed cell death.
Toxicol Pathol, 35 (2007), pp. 495-516
[9.]
A.G. Uren, K. O’Rourke, L.A. Aravind, et al.
Identification of paracaspases and metacaspases: two ancient families of caspaselike proteins, one of which plays a key role in MALT lymphoma.
Mol Cell, 6 (2000), pp. 961-967
[10.]
N. Watanabe, E. Lam.
Two arabidopsis metacaspases AtMCP1b and AtMCP2b are arginine/lysine-specific cysteine proteases and activate apoptosis-like cell death in yeast.
J Biol Chem, 280 (2005), pp. 14691-14699
[11.]
I.J. González, C. Desponds, C. Schaff, et al.
Leishmania major metacaspase can replace yeast metacaspase in programmed cell death and has arginine-specific cysteine peptidase activity.
Int J Parasitol, 37 (2007), pp. 161-172
[12.]
Q. Liang, W. Li, B. Zhou.
Caspase-independent apoptosis in yeast.
Biochim Biophys Acta, 1783 (2008), pp. 1311-1319
[13.]
S. Büttner, T. Eisenberg, E. Herker, et al.
Why yeast cells can undergo apoptosis: death in times of peace, love, and war.
J Cell Biol, 175 (2006), pp. 521-525
[14.]
M.F. Suarez, L.H. Filonova, A. Smertenko, et al.
Metacaspase-dependent programmed cell death is essential for plant embryogenesis.
Curr Biol, 14 (2004), pp. 339-340
[15.]
F.A. Hoeberichts, A. ten Have, E.J. Woltering.
A tomato metacaspase gene is upregulated during programmed cell death in Botrytis cinerea-infected leaves.
Planta, 217 (2003), pp. 517-522
[16.]
G. Kosec, V.E. Álvarez, F. Aguero, et al.
Metacaspases of Trypanosoma cruzi: possible candidates for programmed cell death mediators.
Mol Biochem Parasitol, 145 (2006), pp. 18-28
[17.]
A. Szallies, B.K. Kubata, M. Duszenko.
A metacaspase of Trypanosoma brucei causes loss of respiration competence and clonal death in the yeast Saccharomyces cerevisiae.
FEBS Lett., 517 (2002), pp. 144-150
[18.]
P. Mukherjee, S.B. Majee, S. Ghosh, et al.
Apoptosis-like death in Leishmania donovani promastigotes induced by diospyrin and its ethanolamine derivative.
Int J Antimicrob Agents, 34 (2009), pp. 596-601
[19.]
M. Das, S.B. Mukherjee, C. Shaha.
Hydrogen peroxide induces apoptosis-like death in Leishmania donovani promastigotes.
J Cell Sci, 114 (2001), pp. 2461-2469
[20.]
J. Mishra, A. Saxena, S. Singh.
Chemotherapy of leishmaniasis: past, present and future.
Curr Med Chem, 14 (2007), pp. 1153-1169
[21.]
C. Shaha.
Apoptosis in ispecies & its relevance to disease pathogenesis.
Indian J Med Res, 123 (2006), pp. 233-244
[22.]
N.K. Verma, C.S. Dey.
Possible mechanism of miltefosine-mediated death of Leishmania donovani.
Antimicrob Agents Chemother, 48 (2004), pp. 3010-3015
[23.]
P. Desjeux, Leishmaniasis:.
current situation and new perspectives.
Comp Immunol Microbiol Infect Dis, 27 (2004), pp. 305-318
[24.]
C. Paris, P.M. Loiseau, C. Bories, et al.
Miltefosine induces apoptosis-like death in Leishmania donovani promastigotes.
Antimicrob Agents Chemother, 48 (2004), pp. 852-859
[25.]
M. Lamkanfi, N. Festjens, W. Declercq, et al.
Caspases in cell survival, proliferation and differentiation.
Cell Death Differ, 14 (2006), pp. 44-55
[26.]
A. Ambit, N. Fasel, G.H. Coombs, et al.
An essential role for the Leishmania major metacaspase in cell cycle progression.
Cell Death Differ, 15 (2008), pp. 113-122
[27.]
L. Arvind, V.M. Dixit, E.V. Konin.
Apoptotic molecular machinery: vastly increased complexity in vertebrates revealed by genome comparisons.
Science, 291 (2001), pp. 1279-1284
[28.]
G. Singh, K.G. Jayanarayan, C.S. Dey.
Novobiocin induces apoptosis-like cell death in topoisomerase II over-expressing arsenite resistant Leishmania donovani.
Mol Biochem Parasitol, 141 (2005), pp. 57-69
[29.]
S. Khademvatan, M.J. Gharavi, L. Akhlaghi, et al.
Induction of apoptosis by miltefosine in Iranian strain of Leishmania infantum promastigotes.
Iranian J Parasitol, 4 (2009), pp. 23-31
Copyright © 2011. Elsevier Editora Ltda.. All rights reserved
Download PDF
The Brazilian Journal of Infectious Diseases
Article options
Tools