Cell death in Leishmania induced by stress and differentiation: programmed cell death or necrosis?

Cell Death Differ. 2002 Oct;9(10):1126-39. doi: 10.1038/sj.cdd.4401071.

Abstract

Unicellular organisms, such as the protozoan parasite Leishmania, can be stimulated to show some morphological and biochemical features characteristic of mammalian apoptosis. This study demonstrates that under a variety of stress conditions such as serum deprivation, heat shock and nitric oxide, cell death can be induced leading to genomic DNA fragmentation into oligonucleosomes. DNA fragmentation was observed, without induction, in the infectious stages of the parasite, and correlated with the presence of internucleosomal nuclease activity, visualisation of 45 to 59 kDa nucleases and detection of TUNEL-positive nuclei. DNA fragmentation was not dependent on active effector downstream caspases nor on the lysosomal cathepsin L-like enzymes CPA and CPB. These data are consistent with the presence of a caspase-independent cell death mechanism in Leishmania, induced by stress and differentiation that differs significantly from metazoa.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / physiology*
  • Caspases / metabolism
  • Cell Differentiation / physiology*
  • Cell Nucleus / drug effects
  • Cell Nucleus / enzymology
  • Cell Nucleus / ultrastructure
  • Cells, Cultured
  • Chelating Agents / pharmacology
  • Coumarins / pharmacology
  • DNA / drug effects
  • DNA / metabolism
  • DNA Fragmentation / physiology
  • Electrophoresis, Polyacrylamide Gel
  • Endonucleases / drug effects
  • Endonucleases / metabolism
  • Humans
  • In Situ Nick-End Labeling
  • Leishmania / drug effects
  • Leishmania / metabolism*
  • Leishmania / ultrastructure
  • Leishmaniasis / metabolism*
  • Leishmaniasis / physiopathology
  • Mice
  • Microscopy, Electron
  • Oligopeptides / pharmacology
  • Stress, Physiological / metabolism*
  • Stress, Physiological / physiopathology

Substances

  • Chelating Agents
  • Coumarins
  • Oligopeptides
  • acetyl-aspartyl-glutamyl-valyl-aspartyl-amino-4-methylcoumarin
  • DNA
  • Endonucleases
  • Caspases