Hydrogen peroxide-mediated toxicity for Leishmania donovani chagasi promastigotes: Role of hydroxyl radical and protection by heat shock

J. H. Zarley, B. E. Britigan, M. E. Wilson

Research output: Contribution to journalArticle

91 Citations (Scopus)

Abstract

Leishmania must survive despite exposure to the toxic oxidant hydrogen peroxide (H2O2) during phagocytosis by macrophages. We investigated the mechanism of H2O2 toxicity for L. donovani chagasi promastigotes, and factors responsible for their relative H2O2 resistance. There was a dose-dependent toxic effect of H2O2 for promastigotes isolated during logarithmic phase of growth. In contrast, stationary phase promastigotes were less susceptible to H2O2 toxicity, and more infectious for BALB/c mice. By spin trapping we found that hydroxyl radical (·OH) was generated after exposure of promastigotes to H2O2, and the amount of ·OH was greater with log-phase than with stationary-phase promastigotes. ·OH was generated after the addition of H2O2 to the cytosol but not the membranes of fractionated promastigotes, and the magnitude of ·OH was greater in log than in stationary promastigote cytosol. Deferoxamine inhibition suggested that intracellular promastigote iron catalyzes ·OH formation via the Fenton reaction. Furthermore, exposure of log-phase promastigotes to heat shock induced a relative H2O2-resistant state, which was not associated with a decrease in ·OH formation but which required ongoing transcription. Thus, growth to stationary phase and heat shock both induce a state of relative H2O2 resistance, but these are probably due to different resistance mechanisms.

Original languageEnglish (US)
Pages (from-to)1511-1521
Number of pages11
JournalJournal of Clinical Investigation
Volume88
Issue number5
DOIs
StatePublished - Jan 1 1991

Fingerprint

Leishmania infantum
Poisons
Hydroxyl Radical
Cytosol
Hydrogen Peroxide
Shock
Hot Temperature
Spin Trapping
Deferoxamine
Leishmania
Growth
Phagocytosis
Oxidants
Iron
Macrophages
Membranes

Keywords

  • Electron paramagnetic resonance spectrometry (EPR)
  • Intracellular parasite
  • Macrophage
  • Spin trapping
  • Virulence factors

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Hydrogen peroxide-mediated toxicity for Leishmania donovani chagasi promastigotes : Role of hydroxyl radical and protection by heat shock. / Zarley, J. H.; Britigan, B. E.; Wilson, M. E.

In: Journal of Clinical Investigation, Vol. 88, No. 5, 01.01.1991, p. 1511-1521.

Research output: Contribution to journalArticle

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