Electrospray ionization and tandem mass spectrometry of eicosanoids

Murphy, Robert C.; Barkley, Robert M.; Berry, Karin Zemski; Hankin, Joseph A.; Harrison, Kathleen A.; Johnson, Chris; Krank, Jessica; McAnoy, Andrew M.; Uhlson, Charis L.; Zarini, Simona

doi:10.1016/j.ab.2005.04.042

Cited by 220 publications

(252 citation statements)

References 141 publications

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“…11␤-PGF 2␣ is an enzymatic product of PGD 2 (action of PGD 2 11-ketoreductase), whereas PGF 2␣ forms directly from PGH 2 (action of PGH 2 9,11-endoperoxide reductase) (21). The peak pattern observed for 11␤-PGF 2␣ , with ([Mϩd 6 ]-H) Ϫ being the most intense peak of the deuterated components and resembling the pattern obtained for PGD 2 ( Fig. 2A), supports that it does indeed originate from PGD 2 .…”

Section: Dimples/ms Reveals Differing Mechanistic Origins and Metabolsupporting

confidence: 54%

“…2A). The formation of a ketone group on C-11 of PGD 2 (Fig. 2B) requires the loss of a deuterium atom from this position of its AA-d 8 precursor (Fig.…”

Section: Aa-dmentioning

confidence: 99%

“…More recent advances in electrospray ionization-MS coupled to high-performance liquid chromatography have offered extremely sensitive and quantitative assays for most of the eicosanoids (2), without the need for chemical derivatization prior to analysis as was required by earlier gas chromatography electron ionization-MS methods (3). It is important to recognize, however, that while advances in high-performance LC-MS methods have offered extensive capabilities for surveying a number of different eicosanoid species in a single analysis, to date most efforts have focused on a specific eicosanoid or eicosanoid class, and additionally, with advanced knowledge and assumptions as to the identity of these species (4 -11).…”

mentioning

confidence: 99%

“…adrenic acid, 7Z,10Z,13Z,16Z-docosatetraenoic acid; COX, cyclooxygenase; DiHETE, dihydroxy-eicosatetraenoic acid; DIMPLES/MS, diverse isotope metabolic profiling of labeled exogenous substrates using mass spectrometry; HETE, hydroxyeicosatetraenoic acid; HpETE, hydroperoxyeicosatetraenoic acid; Kdo 2 -Lipid A, (3-deoxy-D-mannooctulosonic acid) 2 -Lipid A; LC-RT, liquid chromatography-retention time; MS/MS, tandem mass spectrometry; MRM, multiple reaction monitoring; PGD 2 , prostaglandin D 2 (9S,15S-dihydroxy-11-oxo-5Z,13E-prostadienoic acid); PGE 2 , prostaglandin E 2 (9-oxo-11R,15S-dihydroxy-5Z,13E-prostadienoic acid); PGF 2␣ , prostaglandin F 2␣ (9S,11R,15S-trihydroxy-5Z,13E-prostadienoic acid); PGG 2 , prostaglandin G 2 (9S,11R-epidioxy-15S-hydroperoxy-5Z,13E-prostadienoic acid); PGH 2 , prostaglandin H 2 (9S,11R-epidioxy-15S-hydroxy-5Z,13E-prostadienoic acid); PGJ 2 , prostaglandin J 2 (11-oxo-15S-hydroxy-5Z,8Z,13E-prostatrienoic acid); 11␤-PGF 2␣ (9S,11S,15S-trihydroxy-5Z,13E-prostadienoic acid); 15d-⌬ 12,14 -PGD 2 , 15-deoxy-prostaglandin D 2 (11-oxo-9S-hydroxy-5Z,12E,14E-prostatrienoic acid); 15d-⌬ 12,14 -PGJ 2 , 15-deoxyprostaglandin J 2 (11-oxo-5Z,9,12E,14Z-prostatetraenoic acid); dihomoprostaglandin, 1a,1b-dihomologue prostaglandin; dihomo-PGD 2 , dihomoprostaglandin D 2 (1a,1b-dihomo-9S,15S-dihydroxy-11-oxo-5Z,13E-prostadienoic acid); dihomo-PGE 2 , dihomoprostaglandin E 2 (1a,1b-dihomo-9-oxo-11R,15S-dihydroxy-5Z,13E-prostadienoic acid); dihomo-PGF 2␣ , dihomoprostaglandin F 2␣ (1a,1b-dihomo-9S,11R,15S-trihydroxy-5Z,13E-prostadienoic acid); dihomo-PGJ 2 , dihomoprostaglandin J 2 (1a,1b-dihomo-11-oxo-15S-hydroxy-5Z,8Z,13E-prostatrienoic acid); dihomo-15d-⌬ 12,14 -PGD 2 , dihomo-15-deoxyprostaglandin D 2 (1a,1b-dihomo-9S-hydroxy-11-oxo-5Z,12E,14E-prostatrienoic acid).…”

mentioning

confidence: 99%

“…: 858-534-3055; Fax: 858-534-7390; E-mail: edennis@ucsd.edu. 2 The abbreviations used are: MS, mass spectrometry; AA, arachidonic acid (5Z,8Z,11Z,14Z-eicosatetraenoic acid); AA-d 8 , deuterated-AA (octadeuterated AA, 5Z,8Z,11Z,14Z-eicosatetraenoic acid, 5,6,8,9,11,12,14,15-d 8 );…”

mentioning

confidence: 99%

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Arachidonate-derived Dihomoprostaglandin Production Observed in Endotoxin-stimulated Macrophage-like Cells

Harkewicz

Fahy

Andreyev

et al. 2007

Journal of Biological Chemistry

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Eicosanoids, including the prostaglandins, leukotrienes, hydroxyeicosatetraenoic acids, epoxyeicosatetraenoic acids, and related compounds, are biosynthetic, bioactive mediators derived from arachidonic acid (AA), a 20:4(n-6) fatty acid. We have developed a comprehensive and sensitive mass spectral analysis to survey eicosanoid release from endotoxin-stimulated RAW 264.7 macrophage-like cells that is capable of detecting over 70 diverse eicosanoids and eicosanoid metabolites, should they be present. We now address the question: Are biologically significant eicosanoids being overlooked? Herein, we illustrate a general approach to diverse isotope metabolic profiling of labeled exogenous substrates using mass spectrometry (DIM-PLES/MS), demonstrated for one substrate (AA) and its resultant products (eicosanoids). RAW cells were incubated in medium supplemented with deuterium-labeled AA. When the cells are stimulated, two sets of eicosanoids are produced, one from endogenous AA and the other from the supplemented (exogenous) deuterium-labeled form. This produces a signature mass spectral "doublet" pattern, allowing for a comprehensive and diverse eicosanoid search requiring no previous knowledge or assumptions as to what these species may be, in contrast to traditional methods. We report herein observing unexpected AA metabolites generated by the cells, some of which may constitute novel bioactive eicosanoids or eicosanoid inactivation metabolites, as well as demonstrating differing metabolic pathways for the generation of isomeric prostaglandins and potential peroxisome proliferator-activated receptor activators. Unexpectedly, we report observing a series of 1a,1b-dihomologue prostaglandins, products of adrenic acid (22:4(n-6)), resulting from the two-carbon elongation of AA by the RAW cells.Starting in the early 1960s with the first structural characterization of the prostaglandins (1), mass spectrometry (MS) 2 has played a critical role in the biochemical study of eicosanoids. More recent advances in electrospray ionization-MS coupled to high-performance liquid chromatography have offered extremely sensitive and quantitative assays for most of the eicosanoids (2), without the need for chemical derivatization prior to analysis as was required by earlier gas chromatography electron ionization-MS methods (3). It is important to recognize, however, that while advances in high-performance LC-MS methods have offered extensive capabilities for surveying a number of different eicosanoid species in a single analysis, to date most efforts have focused on a specific eicosanoid or eicosanoid class, and additionally, with advanced knowledge and assumptions as to the identity of these species (4 -11). Recently, however, investigators have begun to explore the development of theoretical databases and algorithms based on virtual liquid chromatography-UV spectroscopy-tandem mass spectrometry (MS/MS) spectra and chromatograms for identifying potential lipid mediators without synthetic or authentic products as standards (12).System...

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Section: Dimples/ms Reveals Differing Mechanistic Origins and Metabolsupporting

confidence: 54%

“…2A). The formation of a ketone group on C-11 of PGD 2 (Fig. 2B) requires the loss of a deuterium atom from this position of its AA-d 8 precursor (Fig.…”

Section: Aa-dmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Arachidonate-derived Dihomoprostaglandin Production Observed in Endotoxin-stimulated Macrophage-like Cells

Harkewicz

Fahy

Andreyev

et al. 2007

Journal of Biological Chemistry

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Metabolomics‐Lipidomics of Eicosanoids and Docosanoids Generated by Phagocytes

et al. 2011

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Lipid mediators derived from essential fatty acids such as arachidonic acid play important and sometimes pivotal roles in physiologic and pathophysiologic processes. Prostaglandins, thromboxane and leukotrienes are well-known eicosanoids that play a role in hemodynamics and inflammation. More recently, new families of mediators were uncovered that constitute a new genus that stimulate resolution of acute inflammation, are organ-protective and reduce the sequelae of ischemia-reperfusion tissue injury. These include the resolvins (E-series and D-series), protectins (neuroprotectin D1/protectin D1) and maresins biosynthesized from omega-3 essential fatty acids. Phagocytes play a major role in tissues and have a high capacity to produce these mediators, which depend on their tissue and state of activation. Since metabolomic profiling of these biosynthetic pathways in phagocytes can also yield inactive metabolites as well as isomers of specific mediators, it is important to select appropriate methods for identifying target mediators and pathway biomarkers. In this chapter, we review state-of-the-art approaches to identify and profile eicosanoid and docosanoid pathways, including specialized pro-resolving mediators such as resolvins, protectins and maresins that are produced by phagocytes in inflammatory exudates. We provide protocols for isolation and criteria for selecting methods and give examples of metabolomics and lipidomic procedures using liquid chromatography-tandem mass spectrometry-based instrumentation. The approaches reviewed here can provide documentation of bioactive mediators from the eicosanoid and docosanoid-metabolomes in relation to their biosynthesis and inactivation by phagocytes, particularly neutrophils and macrophages.

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Mass Spectrometry for Lipid Analyses

Mesaros

Blair

2008

Wiley Encyclopedia of Chemical Biology

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The increasing recognition that lipids have important biological functions in signal transduction in addition to their structural role in cell membranes has stimulated tremendous activity in the field of lipid research. Their complex structures and the potent biological activity of many individual lipids has necessitated the development of highly specific and sensitive methodology for their analysis. Mass spectrometry (MS)‐based methodology has become the technique of choice because of its ability to conduct analyses on trace amounts of bioactive lipids. Gas chromatography (GC)‐MS was widely used for the early studies on lipid analysis, but the applicability was limited. Development of the new atmospheric pressure ionization (API) techniques and matrix‐assisted laser desorption/ionization (MALDI) has significantly increased the range of lipids that can be analyzed by MS. Methodology based on these ionization techniques will continue to make an important contribution to lipid analysis for the foreseeable future.

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Electrospray ionization and tandem mass spectrometry of eicosanoids

Cited by 220 publications

References 141 publications

Arachidonate-derived Dihomoprostaglandin Production Observed in Endotoxin-stimulated Macrophage-like Cells

Arachidonate-derived Dihomoprostaglandin Production Observed in Endotoxin-stimulated Macrophage-like Cells

Metabolomics‐Lipidomics of Eicosanoids and Docosanoids Generated by Phagocytes

Mass Spectrometry for Lipid Analyses

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