Quantitative Profiling Method for Oxylipins in Neurodegenerative Diseases by Liquid Chromatography Coupled with Tandem Mass Spectrometry.
Quantitative Profiling Method for Oxylipins in Neurodegenerative Diseases by Liquid Chromatography Coupled with Tandem Mass Spectrometry.
复制标题
通过液相色谱与串联质谱联用对神经退行性疾病中的氧脂质进行定量分析。
DOI：
10.1101/2023.10.02.560544
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Lee,KinSingStephen
中科院分区：
文献类型：
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作者：
Pourmand,Elham;Zhang,Fan;Sarparast,Morteza;Alan,JamieK;Lee,KinSingStephen
衰老是许多慢性疾病的主要危险因素之一，包括糖尿病、神经病、高血压、癌症和神经退行性疾病。然而，衰老背后的机制以及衰老如何影响各种疾病的进展仍然未知。近年来的研究表明，细胞色素P450（P450）-环氧化物水解酶（EH）代谢产物多不饱和脂肪酸（PUFAs）在上述年龄相关性疾病中起着关键作用。因此，衰老可能通过调节CYP-EH PUFA代谢而影响上述慢性疾病。不幸的是，研究衰老如何影响人类和哺乳动物模型中的CYP-EH代谢带来了重大挑战。在这方面，我们将使用C。线虫作为模式生物来研究衰老对PUFA的CYP-EH代谢的影响，由于其被用于研究衰老的悠久历史和进行衰老研究的相关益处。本项目将开发分析工具来测量C.使用最先进的超高效液相色谱-串联质谱法（UPLC-MS/MS）对秀丽隐杆线虫进行分析。这些代谢物非常有效，但丰度较低。UPLC-MS/MS灵敏度的显著增加使我们能够在C.用最少的样本。我们的结果表明C.使用我们的SPE-UPLC-MS/MS方法，秀丽线虫产生与哺乳动物和人类相似的PUFA代谢物。我们还将表明，我们的方法成功地确定了CYP-EH PUFA代谢产物的变化引起的抑制C。elegans EH.该项目开发的方法将显著提高我们对膳食PUFA和相关代谢对衰老和神经退行性变的作用的理解，并将揭示衰老如何通过调节PUFA代谢途径影响神经退行性变的新机制。
Aging is one of the major risk factors for many chronic diseases, including diabetes, neuropathy, hypertension, cancer, and neurodegenerative diseases. However, the mechanism behind aging and how aging affects a variety of disease progression remains unknown. Recent research demonstrated the cytochrome P450 (CYP)-epoxide hydrolase (EH) metabolites of polyunsaturated fatty acids (PUFAs) play a critical role in the abovementioned age-associated diseases. Therefore, aging could affect the abovementioned chronic diseases by modulating CYP-EH PUFA metabolism. Unfortunately, investigating how aging affects CYP-EH metabolism in human and mammalian models poses significant challenges. In this regard, we will use C. elegans as a model organism to investigate the aging effects on CYP-EH metabolism of PUFA, owing to its long history of being used to study aging and its associated benefits of conducting aging research. This project will develop analytical tools to measure the endogenous levels of CYP-EH PUFA metabolites in C. elegans using state-of-the-art ultra-performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS). These metabolites are very potent but present in low abundance. The dramatic increase in sensitivity in UPLC-MS/MS allows us to monitor these metabolites over the lifespan of C. elegans with minimum samples. Our results show that C. elegans produces similar CYP PUFA metabolites to mammals and humans using our SPE-UPLC-MS/MS method. We will also show that our method successfully determined the CYP-EH PUFA metabolites profile changes induced by the inhibition of C. elegans EH. The method developed from this project will significantly improve our understanding of the role of dietary PUFAs and associated metabolism on aging and neurodegeneration and will uncover new mechanisms of how aging affects neurodegeneration through the modulation of PUFA metabolic pathways.