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Article

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

1
Departamento de Fisiologia, Instituto de Biociências, Universidade de São Paulo, São Paulo, SP 05508-090, Brazil
2
Centre for Metabolomics and Bioanalysis (CEMBIO), Departamento de Química e Bioquímica, Facultad de Farmacia, Universidad CEU San Pablo, Campus Monteprincipe, Boadilla del Monte, 28660 Madrid, Spain
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2019, 20(24), 6248; https://doi.org/10.3390/ijms20246248
Received: 5 November 2019 / Revised: 6 December 2019 / Accepted: 8 December 2019 / Published: 11 December 2019
(This article belongs to the Special Issue Arginine Metabolism)
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. View Full-Text
Keywords: polyamines pathway; metabolites; bone marrow-derived macrophages; arginine polyamines pathway; metabolites; bone marrow-derived macrophages; arginine
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MDPI and ACS Style

Muxel, S.M.; Mamani-Huanca, M.; Aoki, J.I.; Zampieri, R.A.; Floeter-Winter, L.M.; López-Gonzálvez, Á.; Barbas, C. Metabolomic Profile of BALB/c Macrophages Infected with Leishmania amazonensis: Deciphering L-Arginine Metabolism. Int. J. Mol. Sci. 2019, 20, 6248. https://doi.org/10.3390/ijms20246248

AMA Style

Muxel SM, Mamani-Huanca M, Aoki JI, Zampieri RA, Floeter-Winter LM, López-Gonzálvez Á, Barbas C. Metabolomic Profile of BALB/c Macrophages Infected with Leishmania amazonensis: Deciphering L-Arginine Metabolism. International Journal of Molecular Sciences. 2019; 20(24):6248. https://doi.org/10.3390/ijms20246248

Chicago/Turabian Style

Muxel, Sandra M., Maricruz Mamani-Huanca, Juliana I. Aoki, Ricardo A. Zampieri, Lucile M. Floeter-Winter, Ángeles López-Gonzálvez, and Coral Barbas. 2019. "Metabolomic Profile of BALB/c Macrophages Infected with Leishmania amazonensis: Deciphering L-Arginine Metabolism" International Journal of Molecular Sciences 20, no. 24: 6248. https://doi.org/10.3390/ijms20246248

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