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Ultra performance liquid chromatography - mass spectrometry studies of formalin-induced alterations of human brain lipidome

机译:超高效液相色谱-质谱法研究福尔马林诱导的人脑脂质组改变

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摘要

The development of omics' sciences offers new opportunities for the study of neurodegenerative diseases but increases at the same time the sample demand on brain banks that collect and store valuable human post-mortem tissue. Our study aims to evaluate in lipidomics the potential of formalin-fixed tissue compared with the cryopreservation method, considered as the gold standard for biochemical research. Two complementary liquid chromatography/mass spectrometry analytical platforms were used on the basis of hybrid quadrupole time-of-flight and triple quadrupole mass spectrometers. Untargeted fingerprinting, semitargeted profiling of specific lipid classes and targeted monitoring of lipid species were performed in formalin-fixed and cryopreserved samples to provide detailed information at the molecular level on the formalin-induced alterations of the brain tissue. In vitro incubations of lipid standards were also performed to further describe the degradation processes induced by formaldehyde. Phospholipid compounds were found to be extensively hydrolysed, whilst the sphingolipid ones were preserved. N-methylation and N-formylation of amine-containing phospholipids have also been evidenced. These findings show that the potential detrimental effect of formalin on the analytes of interest must be taken into account when analysing formalin-fixed samples. Copyright (c) 2014 John Wiley & Sons, Ltd.
机译:组学科学的发展为神经退行性疾病的研究提供了新的机会,但同时又增加了对收集和储存有价值的人类尸体组织的脑库的样本需求。我们的研究旨在评估脂质组学中福尔马林固定组织与冷冻保存方法(被认为是生化研究的金标准)相比的潜力。在混合四极杆飞行时间和三重四极杆质谱仪的基础上,使用了两个互补的液相色谱/质谱分析平台。在福尔马林固定和冷冻保存的样品中进行了非靶向指纹分析,特定脂质类别的半靶向分析以及脂质种类的靶向监测,以提供有关福尔马林诱导的脑组织改变的分子水平的详细信息。还进行了脂质标准品的体外温育,以进一步描述甲醛诱导的降解过程。发现磷脂化合物被广泛水解,而鞘脂化合物则被保留。还已经证明了含胺磷脂的N-甲基化和N-甲酰化。这些发现表明,在分析福尔马林固定样品时,必须考虑福尔马林对目标分析物的潜在有害作用。版权所有(c)2014 John Wiley&Sons,Ltd.

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