Metabolomics profiling of the free and total oxidised lipids in urine by LC-MS/MS: application in patients with rheumatoid arthritis

被引:30
作者
Fu, Junzeng [1 ,2 ]
Schoeman, Johannes C. [1 ,3 ]
Harms, Amy C. [1 ,3 ]
van Wietmarschen, Herman A. [2 ,4 ]
Vreeken, Rob J. [1 ,3 ,5 ]
Berger, Ruud [1 ,3 ]
Cuppen, Bart V. J. [6 ]
Lafeber, Floris P. J. G. [6 ]
van der Greef, Jan [1 ,2 ,3 ,4 ]
Hankemeier, Thomas [1 ,3 ]
机构
[1] Leiden Univ, Leiden Acad Ctr Drug Res, Dept Analyt Biosci, Einsteinweg 55, NL-2333 CC Leiden, Netherlands
[2] Sino Dutch Ctr Prevent & Personalized Med, POB 360, NL-3700 AJ Zeist, Netherlands
[3] Leiden Univ, Netherlands Metabol Ctr, Einsteinweg 55, NL-2333 CC Leiden, Netherlands
[4] TNO, Netherlands Org Appl Sci Res Microbiol & Syst Bio, POB 360, NL-3700 AJ Zeist, Netherlands
[5] Janssen R&D, Discovery Sci, Turnhoutseweg 30, B-2340 Beerse, Belgium
[6] Univ Med Ctr Utrecht, Rheumatol & Clin Immunol, F02-127,Heidelberglaan 100, NL-3584 CX Utrecht, Netherlands
关键词
LC-MS/MS; Metabolomics; Oxidized lipids; Urine; beta-glucuronidase; SOLID-PHASE EXTRACTION; OXIDATIVE STRESS; GLUCURONIDE CONJUGATE; LIQUID-CHROMATOGRAPHY; ENZYMATIC-HYDROLYSIS; MASS-SPECTROMETRY; FATTY-ACIDS; METABOLITES; PROSTAGLANDINS; QUANTIFICATION;
D O I
10.1007/s00216-016-9742-2
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
Oxidised lipids, covering enzymatic and auto-oxidation-synthesised mediators, are important signalling metabolites in inflammation while also providing a readout for oxidative stress, both of which are prominent physiological processes in a plethora of diseases. Excretion of these metabolites via urine is enhanced through the phase-II conjugation with glucuronic acid, resulting in increased hydrophilicity of these lipid mediators. Here, we developed a bovine liver-beta-glucuronidase hydrolysing sample preparation method, using liquid chromatography coupled to tandem mass spectrometry to analyse the total urinary oxidised lipid profile including the prostaglandins, isoprostanes, dihydroxy-fatty acids, hydroxy-fatty acids and the nitro-fatty acids. Our method detected more than 70 oxidised lipids biosynthesised from two non-enzymatic and three enzymatic pathways in urine samples. The total oxidised lipid profiling method was developed and validated for human urine and was demonstrated for urine samples from patients with rheumatoid arthritis. Pro-inflammatory mediators PGF(2 alpha) and PGF(3 alpha) and oxidative stress markers iPF(2 alpha)- IV, 11-HETE and 14-HDoHE were positively associated with improvement of disease activity score. Furthermore, the anti-inflammatory nitro-fatty acids were negatively associated with baseline disease activity. In conclusion, the developed methodology expands the current metabolic profiling of oxidised lipids in urine, and its application will enhance our understanding of the role these bioactive metabolites play in health and disease.
引用
收藏
页码:6307 / 6319
页数:13
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