Proteome changes associated with Leishmania donovani promastigote adaptation to oxidative and nitrosative stresses

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• 作者：Abul Hasan Sardar^a ; Sudeep Kumar^b ; Ashish Kumar^a ; Bidyut Purkait^a ; Sushmita Das^a ; Abhik Sen^c ; Manish Kumar^a ; Kislay Kumar Sinha^d ; Dharmendra Singh^a ; Asif Equbal^e ; Vahab Ali^e ; Pradeep Das^a ; ^{drpradeep.das@gmail.com}
• 关键词：iTRAQ ; LC&ndash ; MALDI-TOF/TOF-MS ; Redox homeostasis ; Trypanothione metabolism ; Superoxide metabolism
• 刊名：Journal of Proteomics
• 出版年：2013
• 出版时间：9 April, 2013
• 年：2013
• 卷：81
• 期：Complete
• 页码：185-199
• 全文大小：1505 K

文摘

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 ~ 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.