Mass spectrometric analysis of lipid species of human circulating blood cells

Leidl, Katharina; Liebisch, Gerhard; Richter, Dorothea; Schmitz, Gerd

doi:10.1016/j.chemphyslip.2008.05.067

Cited by 13 publications

(18 citation statements)

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“…Two apparently opposite mechanisms might be a protective response against oxidative stress: a low level of polyunsaturated FA through reduced production of potentially toxic oxidation products, and a high content of phosphatidylethanolamine-based plasmalogens (39,47), which is able to scavenge free ROS. Therefore, cells that lack plasmalogens are more susceptible to free radicals (48).…”

Section: Discussionmentioning

confidence: 99%

A Lipidomic Study of Phospholipid Classes and Species in Human Synovial Fluid

Kosinska

Liebisch

Lochnit

et al. 2013

Arthritis & Rheumatism

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170

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Objective. Membrane phospholipid species contribute to boundary lubrication that is provided by synovial fluid (SF). Altered levels of lubricants can be associated with increased friction, leading to articular cartilage damage. This study was undertaken to determine whether the composition of phospholipid species is altered in diseases of human knee joints.Methods. The study was performed using SF from unaffected controls and patients with early osteoarthritis (OA), late OA, or rheumatoid arthritis (RA). Lipids were extracted from cell-and vesicle-free SF from 9 control donors postmortem and from 17 patients with early OA, 13 patients with late OA, and 18 patients with RA. Phospholipid species were quantified by electrospray ionization tandem mass spectrometry.Results. We conducted lipidomic analysis to provide the first detailed overview of phospholipid species in human SF. We identified 130 lipid species belonging to 8 lipid classes (phosphatidylcholine, lysophosphatidylcholine, phosphatidylethanolamine, plasmalogens, phosphatidylserine, phosphatidylglycerol, sphingomyelin, and ceramide). Compared to SF from controls, SF from patients with early OA and those with late OA had higher levels of most phospholipid species. Moreover, the concentrations of 64 and 27 phospholipids differed between RA and early OA SF and between RA and late OA SF, respectively. Also, the levels of 66 phospholipid species were altered in early OA versus late OA.Conclusion. Our data indicate disease-and stagedependent differences in the relative composition and levels of phospholipid species in human SF. Such alterations might affect articular joint lubrication. Because certain phospholipids scavenge reactive oxygen species (ROS) and are pro-or antiinflammatory, any altered phospholipid level might influence ROS-scavenging activity of SF and the inflammatory status of joints. Thus, phospholipids may be associated with the pathogenesis of OA.

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Section: Discussionmentioning

confidence: 99%

A Lipidomic Study of Phospholipid Classes and Species in Human Synovial Fluid

Kosinska

Liebisch

Lochnit

et al. 2013

Arthritis & Rheumatism

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170

201

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“…The 9 PEth species covered in our LC-MS method with either SIM or SRM detection were selected from the composition of PC molecular species in human erythrocytes (27 ) and the results of previous MS studies identifying 16:0 and 18:1 as the major fatty acid chains in PEth (18,23 ). In agreement with the species distribution for PC (26 ), the present study confirmed 16:0/ 18:1 and 16:0/18:2 as the predominant fatty acid combinations in PEth extracted from human whole blood samples (i.e., mainly erythrocyte membranes (19 )), together making up approximately 60% of total PEth species measured by this method.…”

Section: Discussionmentioning

confidence: 99%

“…Given that PEth originates from PC, the fatty acid composition of PEth is likely to mirror that of PC. The numerous combinations of chain lengths and double bonds enable formation of a large number of PC species (24 ), with 16:0/18:1 (nomenclature for fatty acids ϭ [number of carbons]:[number of double bonds]) and 16:0/ 18:2 being the major fatty acid combinations in PC extracted from human erythrocyte membranes (25)(26)(27).…”

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confidence: 99%

Molecular Species of the Alcohol Biomarker Phosphatidylethanol in Human Blood Measured by LC-MS

2009

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BACKGROUND:The alcohol biomarker phosphatidylethanol (PEth) comprises a group of ethanolderived phospholipids formed from phosphatidylcholine by phospholipase D. The PEth molecular species have a common phosphoethanol head group onto which 2 fatty acid moieties are attached. We developed an electrospray ionization (ESI) LC-MS method for qualitative and quantitative measurement of different PEth species in human blood.

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“…Next, 300 μg protein was resuspended in 1 mL 1× PBS and stored at −80°C until analysis. Lipid analysis in the presence of isotopic labeled or not naturally occurring lipid species as internal standards was performed as described previously (42,43). Detailed methods are provided in SI Materials and Methods.…”

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confidence: 99%

Choline-releasing glycerophosphodiesterase EDI3 drives tumor cell migration and metastasis

Stewart

Marchan

Lesjak

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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126

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Metastasis from primary tumors remains a major problem for tumor therapy. In the search for markers of metastasis and more effective therapies, the tumor metabolome is relevant because of its importance to the malignant phenotype and metastatic capacity of tumor cells. Altered choline metabolism is a hallmark of cancer. More specifically, a decreased glycerophosphocholine (GPC) to phosphocholine (PC) ratio was reported in breast, ovarian, and prostate cancers. Improved strategies to exploit this altered choline metabolism are therefore required. However, the critical enzyme cleaving GPC to produce choline, the initial step in the pathway controlling the GPC/PC ratio, remained unknown. In the present work, we have identified the enzyme, here named EDI3 (endometrial differential 3). Purified recombinant EDI3 protein cleaves GPC to form glycerol-3-phosphate and choline. Silencing EDI3 in MCF-7 cells decreased this enzymatic activity, increased the intracellular GPC/PC ratio, and decreased downstream lipid metabolites. Downregulating EDI3 activity inhibited cell migration via disruption of the PKCα signaling pathway, with stable overexpression of EDI3 showing the opposite effect. EDI3 was originally identified in our screening study comparing mRNA levels in metastasizing and nonmetastasizing endometrial carcinomas. Both Kaplan-Meier and multivariate analyses revealed a negative association between high EDI3 expression and relapse-free survival time in both endometrial (P < 0.001) and ovarian (P = 0.029) cancers. Overall, we have identified EDI3, a key enzyme controlling GPC and choline metabolism. Because inhibition of EDI3 activity corrects the GPC/PC ratio and decreases the migration capacity of tumor cells, it represents a possible target for therapeutic intervention.

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Mass spectrometric analysis of lipid species of human circulating blood cells

Cited by 13 publications

References 0 publications

A Lipidomic Study of Phospholipid Classes and Species in Human Synovial Fluid

A Lipidomic Study of Phospholipid Classes and Species in Human Synovial Fluid

Molecular Species of the Alcohol Biomarker Phosphatidylethanol in Human Blood Measured by LC-MS

Choline-releasing glycerophosphodiesterase EDI3 drives tumor cell migration and metastasis

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