Journal article
Hydrogen peroxide-mediated toxicity for Leishmania donovani chagasi promastigotes. Role of hydroxyl radical and protection by heat shock
The Journal of clinical investigation, Vol.88(5), pp.1511-1521
11/1991
DOI: 10.1172/JCI115461
PMCID: PMC295659
PMID: 1658042
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.
Details
- Title: Subtitle
- Hydrogen peroxide-mediated toxicity for Leishmania donovani chagasi promastigotes. Role of hydroxyl radical and protection by heat shock
- Creators
- Jonathan H Zarley - Veterans Administration Medical Center, Iowa City, IowaBradley E BritiganMary E Wilson
- Resource Type
- Journal article
- Publication Details
- The Journal of clinical investigation, Vol.88(5), pp.1511-1521
- Publisher
- United States
- DOI
- 10.1172/JCI115461
- PMID
- 1658042
- PMCID
- PMC295659
- ISSN
- 0021-9738
- eISSN
- 1558-8238
- Grant note
- AI28412 / NIAID NIH HHS AI-00832 / NIAID NIH HHS HL44275 / NHLBI NIH HHS
- Language
- English
- Date published
- 11/1991
- Academic Unit
- Microbiology and Immunology; International Programs; Epidemiology; Internal Medicine
- Record Identifier
- 9984001203802771
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