Untargeted Metabolomics Reveal Lipid Alterations upon 2-Deoxyglucose Treatment in Human HaCaT Keratinocytes,Journal of Proteome Research

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Untargeted Metabolomics Reveal Lipid Alterations upon 2-Deoxyglucose Treatment in Human HaCaT Keratinocytes
Journal of Proteome Research ( IF 3.8 ) Pub Date : 2018-02-21 00:00:00 , DOI: 10.1021/acs.jproteome.7b00805
Pierre Le Pogam ₁ , Mickael Doué ₁ , Yann Le Page ₂ , Denis Habauzit ₂ , Maxim Zhadobov ₁ , Ronan Sauleau ₁ , Yves Le Dréan ₂ , David Rondeau _{1,

3}

Affiliation

The glucose analogue 2-deoxyglucose (2-DG) impedes cancer progression in animal models and is currently being assessed as an anticancer therapy, yet the mode of action of this drug of high clinical significance has not been fully delineated. In an attempt to better characterize its pharmacodynamics, an integrative UPLC-Q-Exactive-based joint metabolomic and lipidomic approach was undertaken to evaluate the metabolic perturbations induced by this drug in human HaCaT keratinocyte cells. R-XCMS data processing and subsequent multivariate pattern recognition, metabolites identification, and pathway analyses identified eight metabolites that were most significantly changed upon a 3 h 2-DG exposure. Most of these dysregulated features were emphasized in the course of lipidomic profiling and could be identified as ceramide and glucosylceramide derivatives, consistently with their involvement in cell death programming. Even though metabolomic analyses did not generally afford such clear-cut dysregulations, some alterations in phosphatidylcholine and phosphatidylethanolamine derivatives could be highlighted as well. Overall, these results support the adequacy of the proposed analytical workflow and might contribute to a better understanding of the mechanisms underlying the promising effects of 2-DG.

中文翻译：

非靶向代谢组学揭示了人HaCaT角质形成细胞中2-脱氧葡萄糖治疗后的脂质变化

葡萄糖类似物2-脱氧葡萄糖（2-DG）会阻止动物模型中的癌症进展，目前正被评估为一种抗癌疗法，但该药物具有高临床意义的作用方式尚未完全阐明。为了更好地表征其药效学，采用了基于UPLC-Q-Exactive的联合代谢组学和脂质组学方法来评估该药物在人HaCaT角质形成细胞中引起的代谢扰动。R-XCMS数据处理以及随后的多元模式识别，代谢物识别和途径分析，确定了8个2-DG暴露后变化最大的八种代谢物。这些失调的特征大多数都在脂质组分析过程中得到了强调，可以被确定为神经酰胺和葡萄糖基神经酰胺衍生物，与它们参与细胞死亡程序设计一致。即使代谢组学分析通常不能提供这种明显的异常调节，磷脂酰胆碱和磷脂酰乙醇胺衍生物的某些改变也可以被强调。总体而言，这些结果支持了所提出的分析工作流程的充分性，并且可能有助于更好地理解2-DG潜在效应的潜在机制。磷脂酰胆碱和磷脂酰乙醇胺衍生物的一些改变也可以被强调。总体而言，这些结果支持了所提出的分析工作流程的充分性，并且可能有助于更好地理解2-DG潜在效应的潜在机制。磷脂酰胆碱和磷脂酰乙醇胺衍生物的一些改变也可以被强调。总体而言，这些结果支持了所提出的分析工作流程的充分性，并且可能有助于更好地理解2-DG潜在效应的潜在机制。

更新日期：2018-02-22

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