Inducible resistance to oxidant stress in the protozoan Leishmania chagasi

Melissa A Miller; Stephen E McGowan; Kira R Gantt; Matthew Champion; Sherry L Novick; Kurt A Andersen; Cyrus J Bacchi; Nigel Yarlett; Bradley E Britigan; Mary E Wilson

doi:10.1074/jbc.M003671200

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Inducible resistance to oxidant stress in the protozoan Leishmania chagasi

Journal article

Open access

Peer reviewed

Inducible resistance to oxidant stress in the protozoan Leishmania chagasi

Melissa A Miller, Stephen E McGowan, Kira R Gantt, Matthew Champion, Sherry L Novick, Kurt A Andersen, Cyrus J Bacchi, Nigel Yarlett, Bradley E Britigan and Mary E Wilson

The Journal of biological chemistry, Vol.275(43), pp.33883-33889

10/27/2000

DOI: 10.1074/jbc.M003671200

PMID: 10931831

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Abstract

Leishmania sp. protozoa are introduced into a mammalian skin by a sandfly vector, whereupon they encounter increased temperature and toxic oxidants generated during phagocytosis. We studied the effects of 37 degrees C "heat shock" or sublethal menadione, which generates superoxide and hydrogen peroxide, on Leishmania chagasi virulence. Both heat and menadione caused parasites to become more resistant to H(2)O(2)-mediated toxicity. Peroxide resistance was also induced as promastigotes developed in culture from logarithmic to their virulent stationary phase form. Peroxide resistance was not associated with an increase in reduced thiols (trypanothione and glutathione) or increased activity of ornithine decarboxylase, which is rate-limiting in trypanothione synthesis. Membrane lipophosphoglycan increased in size as parasites developed to stationary phase but not after environmental exposures. Instead, parasites underwent a heat shock response upon exposure to heat or sublethal menadione, detected by increased levels of HSP70. Transfection of promastigotes with L. chagasi HSP70 caused a heat-inducible increase in resistance to peroxide, implying it is involved in antioxidant defense. We conclude that leishmania have redundant mechanisms for resisting toxic oxidants. Some are induced during developmental change and others are induced in response to environmental stress.

Oxidative Stress

Hydrogen Peroxide - toxicity

Sulfhydryl Compounds - metabolism

Animals

Ornithine Decarboxylase - biosynthesis

Leishmania infantum - drug effects

Glycosphingolipids - metabolism

Antioxidants - pharmacology

Leishmania infantum - metabolism

HSP70 Heat-Shock Proteins - biosynthesis

Details

Title: Subtitle: Inducible resistance to oxidant stress in the protozoan Leishmania chagasi
Creators: Melissa A Miller - Veterans Affairs Medical Center, the Departments of Internal Medicine and Microbiology, and the Interdisciplinary Immunology Program, University of Iowa, Iowa City, Iowa 52242, USA
Stephen E McGowan
Kira R Gantt
Matthew Champion
Sherry L Novick
Kurt A Andersen
Cyrus J Bacchi
Nigel Yarlett
Bradley E Britigan
Mary E Wilson
Resource Type: Journal article
Publication Details: The Journal of biological chemistry, Vol.275(43), pp.33883-33889
DOI: 10.1074/jbc.M003671200
PMID: 10931831
NLM abbreviation: J Biol Chem
ISSN: 0021-9258
eISSN: 1083-351X
Publisher: United States
Grant note: DK/AI52550 / NIDDK NIH HHS AI32135 / NIAID NIH HHS AI34954 / NIAID NIH HHS
Language: English
Date published: 10/27/2000
Academic Unit: Microbiology and Immunology; International Programs; Epidemiology; Internal Medicine
Record Identifier: 9983983670302771

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