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非靶向液相色谱-高分辨率质谱代谢组学研究揭示缺乏脂滴蛋白激酶时脂质含量的变化

Untargeted Liquid Chromatography-High-Resolution Mass Spectrometry Metabolomic Investigation Reveals Altered Lipid Content in Lacking Lipid Droplet Protein Kinase.

作者信息

Ribeiro Juliana Martins, Canuto Gisele André Baptista, Caldeira Alisson Samuel Portes, de Siqueira Ezequias Pessoa, Zani Carlos Leomar, Murta Silvane Maria Fonseca, de Almeida Alves Tânia Maria

机构信息

Grupo Genômica Funcional de Parasitos, Instituto René Rachou, Fundação Oswaldo Cruz, Belo Horizonte 30190-002, Minas Gerais, Brazil.

Departamento de Química Analítica, Instituto de Química, Universidade Federal da Bahia, Salvador 40170-115, Bahia, Brazil.

出版信息

Trop Med Infect Dis. 2024 Sep 10;9(9):208. doi: 10.3390/tropicalmed9090208.

DOI:10.3390/tropicalmed9090208
PMID:39330897
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11435790/
Abstract

Leishmaniasis is a complex disease caused by different species of . To date, no vaccine for humans or ideal therapy has been developed owing to the limited efficacy and toxicity of available drugs, as well as the emergence of resistant strains. Therefore, it is necessary to identify novel therapeutic targets and discover therapeutic options for leishmaniasis. In this study, we evaluated the impact of deleting the lipid droplet protein kinase (LDK) enzyme in using an untargeted metabolomics approach performed using liquid chromatography and high-resolution mass spectrometry. LDK is involved in lipid droplet biogenesis in trypanosomatids. Thirty-nine lipid metabolites altered in the stationary and logarithmic growth phases were noted and classified into five classes: (1) sterols, (2) fatty and conjugated acids, (3) ceramides, (4) glycerophosphocholine and its derivatives, and (5) glycerophosphoethanolamine and its derivatives. Our data demonstrated that glycerophosphocholine and its derivatives were the most affected after LDK deletion, suggesting that the absence of this enzyme promotes the remodeling of lipid composition in , thus contributing to a better understanding of the function of LDK in this parasite.

摘要

利什曼病是一种由不同种类的……引起的复杂疾病。由于现有药物疗效有限且有毒性,以及耐药菌株的出现,迄今为止,尚未开发出针对人类的疫苗或理想的治疗方法。因此,有必要确定利什曼病的新型治疗靶点并探索治疗方案。在本研究中,我们使用液相色谱和高分辨率质谱进行的非靶向代谢组学方法,评估了在……中删除脂滴蛋白激酶(LDK)酶的影响。LDK参与锥虫中的脂滴生物合成。记录了在稳定期和对数生长期改变的39种脂质代谢物,并将其分为五类:(1)甾醇,(2)脂肪酸和共轭酸,(3)神经酰胺,(4)甘油磷酸胆碱及其衍生物,以及(5)甘油磷酸乙醇胺及其衍生物。我们的数据表明,删除LDK后,甘油磷酸胆碱及其衍生物受到的影响最大,这表明该酶的缺失促进了……中脂质组成的重塑,从而有助于更好地理解LDK在这种寄生虫中的功能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/63f0/11435790/ccd4cc6e9ac6/tropicalmed-09-00208-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/63f0/11435790/39f953965c3e/tropicalmed-09-00208-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/63f0/11435790/ccd4cc6e9ac6/tropicalmed-09-00208-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/63f0/11435790/39f953965c3e/tropicalmed-09-00208-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/63f0/11435790/ccd4cc6e9ac6/tropicalmed-09-00208-g002.jpg

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本文引用的文献

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PLoS Negl Trop Dis. 2024 Jan 18;18(1):e0011880. doi: 10.1371/journal.pntd.0011880. eCollection 2024 Jan.
2
New insights in photodynamic inactivation of Leishmania amazonensis: A focus on lipidomics and resistance.光动力灭活巴西利什曼原虫的新见解:关注脂质组学和耐药性。
PLoS One. 2023 Sep 15;18(9):e0289492. doi: 10.1371/journal.pone.0289492. eCollection 2023.
3
Metabolomics analysis of visceral leishmaniasis based on urine of golden hamsters.
基于金黄地鼠尿液的内脏利什曼病代谢组学分析。
Parasit Vectors. 2023 Aug 30;16(1):304. doi: 10.1186/s13071-023-05881-3.
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Ethanolaminephosphate cytidylyltransferase is essential for survival, lipid homeostasis and stress tolerance in Leishmania major.乙醇胺磷酸胞苷转移酶对利什曼原虫的生存、脂质动态平衡和应激耐受至关重要。
PLoS Pathog. 2023 Jul 28;19(7):e1011112. doi: 10.1371/journal.ppat.1011112. eCollection 2023 Jul.
5
The sphingolipids ceramide and inositol phosphorylceramide protect the Leishmania major membrane from sterol-specific toxins.鞘氨醇和磷酸化肌醇神经酰胺保护恶性疟原虫膜免受固醇特异性毒素的侵害。
J Biol Chem. 2023 Jun;299(6):104745. doi: 10.1016/j.jbc.2023.104745. Epub 2023 Apr 23.
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