Abstract
In the present study we have demonstrated some features characterizing programmed cell death (PCD) in the unicellular protozoan parasite Leishmania donovani, the causative agent of visceral Leishmaniasis. We report that PCD is initiated in stationary phase cultures of promastigotes and both in actively growing cultures of axenic amastigotes and promastigotes upon treatment with anti Leishmanial drugs (Pentostam and amphotericin B). However, the two cell types respond to antileishmanial drugs differently. The features of PCD in L. donovani promastigotes are nuclear condensation, nicked DNA in the nucleus, DNA ladder formation, increase in plasma membrane permeability, decrease in the mitochondrial membrane potential (ΔΨm) and induction of a PhiPhiLux (PPL)-cleavage activity. PCD in both stationary phase culture and upon induction by amphotericin B resulted first in the decrease of mitochondrial membrane potential followed by simultaneous change in plasma membrane permeability and induction of PPL-cleavage activity. Of the total PPL-cleavage activity, several caspase inhibitors inhibited a significant amount (21–34%). Inhibitors of cathepsin or calpain did not inhibit PPL-cleavage activity. Taken together this study demonstrates that the characteristic features of PCD exist in unicellular protozoan Leishmania donovani. The implication of PCD on the Leishmania pathogenesis is discussed.
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Abbreviations
- PCD:
-
programmed cell death
- TMRE:
-
tetramethylrhodamine ethyl ester
- CCCP:
-
carbonyl cyanide p-trifluoromethoxy-phenylhydrazone
- TUNEL:
-
terminal deoxy uridine triphosphate nick end labeling
- PPL:
-
PhiPhiLux
- ΔΨm:
-
mitochondrial membrane potential
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Acknowledgements
Authors would like to thank Drs. Dwyer and Sacks (NIAID, NIH) for critical reading of the manuscript. We thank Drs. Navdeep Chandel and Gerry Melino for providing helpful suggestions in performing mitochondrial membrane potential experiments. We also thank Dr. Sacks for providing the two strains of Leishmania that were freshly isolated from infected animals.
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Lee, N., Bertholet, S., Debrabant, A. et al. Programmed cell death in the unicellular protozoan parasite Leishmania. Cell Death Differ 9, 53–64 (2002). https://doi.org/10.1038/sj.cdd.4400952
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DOI: https://doi.org/10.1038/sj.cdd.4400952
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