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.
引用
收藏
页数:20
相关论文
共 50 条
  • [1] Zinc and Manganese Imbalances in BALB/c Mice Experimentally Infected with Leishmania (Leishmania) amazonensis
    Sobotyk, Caroline
    Baldissera, Fernanda Giesel
    Rodrigues Junior, Luiz Carlos
    Romao, Pedro Roosevelt Torres
    de Oliveira, Juliana Sorraila
    Dornelles, Guilherme Lopes
    de Andrade, Cinthia Melazzo
    Maciel, Roberto Marinho
    Danesi, Cristiane Cademartori
    Ferreira, Rafael Vicente de Padua
    Bellini, Maria Helena
    Botton, Sonia de Avila
    Vogel, Fernanda Silveira Flores
    Sangioni, Luis Antonio
    ACTA PARASITOLOGICA, 2023, 68 (02) : 447 - 452
  • [2] Zinc and Manganese Imbalances in BALB/c Mice Experimentally Infected with Leishmania (Leishmania) amazonensis
    Caroline Sobotyk
    Fernanda Giesel Baldissera
    Luiz Carlos Rodrigues Junior
    Pedro Roosevelt Torres Romão
    Juliana Sorraila de Oliveira
    Guilherme Lopes Dornelles
    Cinthia Melazzo de Andrade
    Roberto Marinho Maciel
    Cristiane Cademartori Danesi
    Rafael Vicente de Padua Ferreira
    Maria Helena Bellini
    Sônia de Avila Botton
    Fernanda Silveira Flores Vogel
    Luis Antonio Sangioni
    Acta Parasitologica, 2023, 68 : 447 - 452
  • [3] Putrescine supplementation shifts macrophage L-arginine metabolism related-genes reducing Leishmania amazonensis infection
    Zanatta, Jonathan Miguel
    Acuna, Stephanie Maia
    Angelo, Yan de Souza
    Bento, Camilla de Almeida
    Peron, Jean Pierre Schatzman
    Stolf, Beatriz Simonsen
    Muxel, Sandra Marcia
    PLOS ONE, 2023, 18 (03):
  • [4] Proteophosophoglycans Regurgitated by Leishmania-Infected Sand Flies Target the L-Arginine Metabolism of Host Macrophages to Promote Parasite Survival
    Rogers, Matthew
    Kropf, Pascale
    Choi, Beak-San
    Dillon, Rod
    Podinovskaia, Maria
    Bates, Paul
    Mueller, Ingrid
    PLOS PATHOGENS, 2009, 5 (08)
  • [5] Pravastatin modulates macrophage functions of Leishmania (L.) amazonensis-infected BALB/c mice
    Kueckelhaus, Carlos S.
    Kueckelhaus, Selma A. S.
    Tosta, Carlos Eduardo
    Muniz-Junqueira, Maria Imaculada
    EXPERIMENTAL PARASITOLOGY, 2013, 134 (01) : 18 - 25
  • [6] EFFECT OF NATURAL NAPHTHOQUINONES IN BALB/C MICE INFECTED WITH LEISHMANIA-AMAZONENSIS AND L-VENEZUELENSIS
    FOURNET, A
    BARRIOS, AA
    MUNOZ, V
    HOCQUEMILLER, R
    CAVE, A
    TROPICAL MEDICINE AND PARASITOLOGY, 1992, 43 (04): : 219 - 222
  • [7] N-acetyl-L-cysteine reduces the parasitism of BALB/c mice infected with Leishmania amazonensis
    Monteiro, Marta Chagas
    Souza Marques, Fulvia Carina
    Blazius, Rene Darela
    da Silva, Onilda Santos
    Cunha, Fernando de Queiroz
    Bento, Diana Bittencourt
    Torres Romao, Pedro Roosevelt
    PARASITOLOGY RESEARCH, 2008, 102 (04) : 801 - 803
  • [8] N-acetyl-l-cysteine reduces the parasitism of BALB/c mice infected with Leishmania amazonensis
    Marta Chagas Monteiro
    Fúlvia Carina Souza Marques
    Renê Darela Blazius
    Onilda Santos da Silva
    Fernando de Queiroz Cunha
    Diana Bittencourt Bento
    Pedro Roosevelt Torres Romão
    Parasitology Research, 2008, 102 : 801 - 803
  • [9] Efficacy of miltefosine treatment in Leishmania amazonensis-infected BALB/c mice
    Prado Godinho, Joseane Lima
    Simas-Rodrigues, Cintia
    Silva, Rosane
    Uermenyi, Turan Peter
    de Souza, Wanderley
    Fernandes Rodrigues, Juliany Cola
    INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS, 2012, 39 (04) : 326 - 331
  • [10] Evaluation of a chloroquine hydrogel for topical treatment of leishmaniasis in BALB/c mice infected with Leishmania (L.) amazonensis
    Branco Junior, Arlindo Gonzaga
    Fialho, Saara Neri
    Gouveia, Aurileya de Jesus
    Ferreira, Amalia dos Santos
    Martinez, Leandro Do Nascimento
    do Nascimento, Welington da Silva Paula
    Rossi, Norton Rubens Diunior Lucas Pejara
    da Silva, Minelly Azevedo
    Lemke, Mariana Francy Malaquias
    Zepon, Karine Modolon
    Kanis, Luiz Alberto
    Ribeiro, Laerth dos Santos
    Teles, Carolina Bioni Garcia
    3 BIOTECH, 2025, 15 (03)