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

被引:25
作者
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 ]
机构
[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
基金
巴西圣保罗研究基金会;
关键词
polyamines pathway; metabolites; bone marrow-derived macrophages; arginine; MICE LACKING; ARGINASE; RECONSTRUCTION; IL-10; TRANSPORTERS; ACTIVATION; RESISTANCE; MECHANISM;
D O I
10.3390/ijms20246248
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
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页数:20
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