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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Metabolomic Profile of BALB/c Macrophages Infected with Leishmania amazonensis: Deciphering L-Arginine Metabolism

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Author(s):
Marcia Muxel, Sandra [1, 2] ; Mamani-Huanca, Maricruz [2] ; Aoki, Juliana Ide [1] ; Zampieri, Ricardo Andrade [1] ; Floeter-Winter, Lucile Maria [1] ; Lopez-Gonzalvez, Angeles [2] ; Barbas, Coral [2]
Total Authors: 7
Affiliation:
[1] Univ Sao Paulo, Inst Biociencias, Dept Fisiol, BR-05508090 Sao Paulo, SP - Brazil
[2] Univ CEU San Pablo, Ctr Metabol & Bioanal CEMBIO, Dept Quim & Bioquim, Fac Farm, Campus Monteprincipe, Madrid 28660 - Spain
Total Affiliations: 2
Document type: Journal article
Source: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; v. 20, n. 24 DEC 2019.
Web of Science Citations: 0
Abstract

Background: Leishmaniases are neglected tropical diseases that are caused by Leishmania, being endemic worldwide. L-arginine is an essential amino acid that is required for polyamines production on mammal cells. During Leishmania infection of macrophages, L-arginine is used by host and parasite arginase to produce polyamines, leading to parasite survival; or, by nitric oxide synthase 2 to produce nitric oxide leading to parasite killing. Here, we determined the metabolomic profile of BALB/c macrophages that were infected with L. amazonensis wild type or with L. amazonensis arginase knockout, correlating the regulation of L-arginine metabolism from both host and parasite. Methods: The metabolites of infected macrophages were analyzed by capillary electrophoresis coupled with mass spectrometry (CE-MS). The metabolic fingerprints analysis provided the dual profile from the host and parasite. Results: We observed increased levels of proline, glutamic acid, glutamine, L-arginine, ornithine, and putrescine in infected-L. amazonensis wild type macrophages, which indicated that this infection induces the polyamine production. Despite this, we observed reduced levels of ornithine, proline, and trypanothione in infected-L. amazonensis arginase knockout macrophages, indicating that this infection reduces the polyamine production. Conclusions: The metabolome fingerprint indicated that Leishmania infection alters the L-arginine/polyamines/trypanothione metabolism inside the host cell and the parasite arginase impacts on L-arginine metabolism and polyamine production, defining the infection fate. (AU)

FAPESP's process: 17/23519-2 - Analysis of role of miRNAs and transcription factors on the regulation of gene expression of Leishmania amazonensis infected murine macrophages
Grantee:Stephanie Maia Acuna
Support type: Scholarships in Brazil - Doctorate (Direct)
FAPESP's process: 18/23512-0 - The Leishmania-host relationship from the ‘omics’ perspective
Grantee:Lucile Maria Floeter-Winter
Support type: Research Projects - Thematic Grants
FAPESP's process: 18/24693-9 - Integration of signaling mediated by transcription factors, long-noncoding RNAs and microRNAs during immune response agaisnt Leishmania amazonensis infection
Grantee:Sandra Marcia Muxel
Support type: Regular Research Grants
FAPESP's process: 16/03273-6 - Dual transcriptome profiling of murine macrophages infected with Leishmania amazonensis
Grantee:Juliana Ide Aoki
Support type: Scholarships in Brazil - Post-Doctorate