Global and Targeted Metabolomics for Revealing Metabolomic Alteration in Niemann-Pick Disease Type C Model Cells.

IF 3.4 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Metabolites Pub Date : 2024-09-24 DOI:10.3390/metabo14100515

Masahiro Watanabe, Masamitsu Maekawa, Keitaro Miyoshi, Toshihiro Sato, Yu Sato, Masaki Kumondai, Masayoshi Fukasawa, Nariyasu Mano

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Abstract

Background: Niemann-Pick disease type C (NPC) is an inherited disorder characterized by a functional deficiency of cholesterol transport proteins. However, the molecular mechanisms and pathophysiology of the disease remain unknown.

Methods: In this study, we identified several metabolite characteristics of NPC that may fluctuate in a cellular model of the disease, using both global and targeted metabolomic analyses by liquid chromatography/tandem mass spectrometry (LC-MS/MS). Three cell lines, HepG2 cells (wild-type[WT]) and two NPC model HepG2 cell lines in which NPC1 was genetically ablated (knockout [KO]1 and KO2), were used for metabolomic analysis. Data were subjected to enrichment analysis using the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways.

Results: The enrichment analysis of global metabolomics revealed that 8 pathways in KO1 and 16 pathways in KO2 cells were notably altered. In targeted metabolomics for 15 metabolites, 4 metabolites in KO1 and 10 metabolites in KO2 exhibited statistically significant quantitative changes in KO1 or KO2 relative to WT. Most of the altered metabolites were related to creatinine synthesis and cysteine metabolism pathways.

Conclusions: In the future, our objective will be to elucidate the relationship between these metabolic alterations and pathophysiology.

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揭示尼曼-皮克病 C 型模型细胞代谢组变化的全局和靶向代谢组学研究

背景：尼曼-皮克病 C 型（NPC）是一种遗传性疾病，其特征是胆固醇转运蛋白功能缺陷。然而，该病的分子机制和病理生理学仍然未知：在这项研究中，我们通过液相色谱/串联质谱（LC-MS/MS）进行全局和靶向代谢组学分析，确定了鼻咽癌细胞模型中可能波动的几种代谢物特征。代谢组学分析使用了三种细胞系，即 HepG2 细胞（野生型[WT]）和两种 NPC 模型 HepG2 细胞系（其中 NPC1 被基因敲除[KO]1 和 KO2）。利用京都基因组百科全书（KEGG）通路对数据进行了富集分析：结果：全局代谢组学的富集分析表明，KO1和KO2细胞中分别有8条和16条通路发生了显著改变。在15种代谢物的靶向代谢组学中，相对于WT，KO1中的4种代谢物和KO2中的10种代谢物在KO1或KO2中表现出统计学意义上的显著定量变化。大多数改变的代谢物与肌酐合成和半胱氨酸代谢途径有关：今后，我们的目标将是阐明这些代谢改变与病理生理学之间的关系。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Metabolites Biochemistry, Genetics and Molecular Biology-Molecular Biology

CiteScore

5.70

自引率

7.30%

发文量

1070

审稿时长

17.17 days

期刊介绍： Metabolites (ISSN 2218-1989) is an international, peer-reviewed open access journal of metabolism and metabolomics. Metabolites publishes original research articles and review articles in all molecular aspects of metabolism relevant to the fields of metabolomics, metabolic biochemistry, computational and systems biology, biotechnology and medicine, with a particular focus on the biological roles of metabolites and small molecule biomarkers. Metabolites encourages scientists to publish their experimental and theoretical results in as much detail as possible. Therefore, there is no restriction on article length. Sufficient experimental details must be provided to enable the results to be accurately reproduced. Electronic material representing additional figures, materials and methods explanation, or supporting results and evidence can be submitted with the main manuscript as supplementary material.