Journal
JOURNAL OF PROTEOMICS
Volume 81, Issue -, Pages 185-199Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jprot.2013.01.011
Keywords
iTRAQ; LC-MALDI-TOF/TOF-MS; Redox homeostasis; Trypanothione metabolism; Superoxide metabolism
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Funding
- Indian Council of Medical Research, India
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Phagocytic cells produce reactive oxygen and nitrogen species (ROS & RNS) as the most common arsenal to kill intracellular pathogens. Leishmania, an obligate intracellular pathogen also confronts this antimicrobial assault during the early phase of infection but nevertheless is able to survive these attacks and proliferate in macrophage. Adaptation of Leishmania to the toxic effects of ROS and RNS, involves a rapid change in the parasite proteome to combat the host defense response that macrophage mount in combating pathogen. To understand the events associated with combating ROS and RNS species, we performed a proteomic analysis of. L. donovani promastigotes treated with sub-lethal doses of menadione (ROS), S-nitroso-N-acetylpenicillamine (RNS) or combination of both compounds. Proteomic changes triggered by these reagents were evaluated by iTRAQ labeling and subsequent LC-MALDI-TOF/TOf-MS analysis. Across the 3 stress conditions, the quantitative analysis identified changes in the proteins which encompass similar to 20% of the parasite proteome. Major changes were observed in enzymatic machinery of pathways involved in maintaining redox homeostasis, trypanothione metabolism, oxidative phosphorylation, superoxide metabolism, mitochondrial respiration process and other essential metabolic pathways. These observations shed light on how Leishmania promastigotes counter ROS and RNS effects during the initial stage of infection. This article is part of a Special Issue entitled: From protein structures to clinical applications. (C) 2013 Elsevier B.V. All rights reserved.
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