Programmed cell death in the unicellular protozoan parasite Leishmania

Cell Death Differ. 2002 Jan;9(1):53-64. doi: 10.1038/sj.cdd.4400952.


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 (DeltaPsi m) 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.

MeSH terms

  • Amphotericin B / pharmacology*
  • Animals
  • Antimony Sodium Gluconate / pharmacology
  • Antiprotozoal Agents / pharmacology
  • Apoptosis / physiology*
  • Caspases / drug effects
  • Caspases / metabolism*
  • Cell Membrane / drug effects
  • Leishmania donovani / drug effects
  • Leishmania donovani / physiology*
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology
  • Mitochondria / drug effects
  • Mitochondria / physiology*
  • Protease Inhibitors / pharmacology


  • Antiprotozoal Agents
  • Protease Inhibitors
  • Amphotericin B
  • Caspases
  • Antimony Sodium Gluconate