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氧化还原脂质组学技术:大海捞针。

"Redox lipidomics technology: Looking for a needle in a haystack".

机构信息

Department of Environmental and Occupational Health, Pittsburgh, PA, USA.

Department of Environmental and Occupational Health, Pittsburgh, PA, USA; Critical Care Medicine, Pittsburgh, PA, USA.

出版信息

Chem Phys Lipids. 2019 Jul;221:93-107. doi: 10.1016/j.chemphyslip.2019.03.012. Epub 2019 Mar 27.

DOI:10.1016/j.chemphyslip.2019.03.012
PMID:30928338
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6714565/
Abstract

Aerobic life is based on numerous metabolic oxidation reactions as well as biosynthesis of oxygenated signaling compounds. Among the latter are the myriads of oxygenated lipids including a well-studied group of polyunsaturated fatty acids (PUFA) - octadecanoids, eicosanoids, and docosanoids. During the last two decades, remarkable progress in liquid-chromatography-mass spectrometry has led to significant progress in the characterization of oxygenated PUFA-containing phospholipids, thus designating the emergence of a new field of lipidomics, redox lipidomics. Although non-enzymatic free radical reactions of lipid peroxidation have been mostly associated with the aberrant metabolism typical of acute injury or chronic degenerative processes, newly accumulated evidence suggests that enzymatically catalyzed (phospho)lipid oxygenation reactions are essential mechanisms of many physiological pathways. In this review, we discuss a variety of contemporary protocols applicable for identification and quantitative characterization of different classes of peroxidized (phospho)lipids. We describe applications of different types of LCMS for analysis of peroxidized (phospho)lipids, particularly cardiolipins and phosphatidylethanolalmines, in two important types of programmed cell death - apoptosis and ferroptosis. We discuss the role of peroxidized phosphatidylserines in phagocytotic signaling. We exemplify the participation of peroxidized neutral lipids, particularly tri-acylglycerides, in immuno-suppressive signaling in cancer. We also consider new approaches to exploring the spatial distribution of phospholipids in the context of their oxidizability by MS imaging, including the latest achievements in high resolution imaging techniques. We present innovative approaches to the interpretation of LC-MS data, including audio-representation analysis. Overall, we emphasize the role of redox lipidomics as a communication language, unprecedented in diversity and richness, through the analysis of peroxidized (phospho)lipids.

摘要

有氧生活基于许多代谢氧化反应以及含氧信号化合物的生物合成。后者包括为数众多的含氧脂质,包括研究得很好的一组多不饱和脂肪酸 (PUFA) - 十八烷酸、二十烷酸和二十二烷酸。在过去的二十年中,液相色谱-质谱的显著进展导致了含氧 PUFA 含磷酯的特征化方面取得了重大进展,从而指定了脂质组学、氧化还原脂质组学的一个新领域的出现。虽然脂质过氧化的非酶自由基反应主要与急性损伤或慢性退行性过程中典型的异常代谢有关,但新积累的证据表明,酶促(磷酸)脂质氧化反应是许多生理途径的重要机制。在这篇综述中,我们讨论了各种适用于鉴定和定量表征不同类别的过氧化(磷酸)脂质的现代方案。我们描述了不同类型的 LCMS 在两种重要类型的程序性细胞死亡 - 凋亡和铁死亡中分析过氧化(磷酸)脂质,特别是心磷脂和磷脂酰乙醇胺的应用。我们讨论了过氧化磷脂酰丝氨酸在吞噬信号中的作用。我们举例说明了过氧化中性脂质,特别是三酰基甘油,在癌症中的免疫抑制信号中的参与。我们还考虑了通过 MS 成像探索磷脂氧化能力的空间分布的新方法,包括高分辨率成像技术的最新成就。我们提出了解释 LC-MS 数据的创新方法,包括音频表示分析。总的来说,我们强调了氧化还原脂质组学作为一种交流语言的作用,通过分析过氧化(磷酸)脂质,其在多样性和丰富性方面是前所未有的。

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Secondary-Ion Mass Spectrometry Images Cardiolipins and Phosphatidylethanolamines at the Subcellular Level.二次离子质谱成像在亚细胞水平分析心磷脂和磷脂酰乙醇胺。
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Triptolide induces hepatotoxicity by promoting ferroptosis through Nrf2 degradation.雷公藤红素通过降解 Nrf2 诱导铁死亡从而导致肝毒性。
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