Sphingolipidomics: High-throughput, structure-specific, and quantitative analysis of sphingolipids by liquid chromatography tandem mass spectrometry

Merrill, Alfred H.; Sullards, M. Cameron; Allegood, Jeremy C.; Kelly, Samuel; Wang, Elaine

doi:10.1016/j.ymeth.2005.01.009

Cited by 549 publications

(513 citation statements)

References 25 publications

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“…[49][50][51][52][53] Recent evidence has further enriched this model supporting a role for SM in the homeostasis of lipid microdomains at the plasma membrane, often sites of receptor-mediated signaling. Taking advantage of the identification of SMS1 as bona fide SM synthase, the role of SM in the activation of Fas signaling was investigated by Miyaji et al 75 Comparing SMS1 deficient cells (with over expressed Fas receptor) with cells in which expression of SMS1 was restored, the authors provide evidence for a critical role of SM in Fas-mediated signaling by enabling the formation of the death-inducing signaling complex (DISC) and consequently allowing caspase activation and production of ceramide at the plasma membrane.…”

Section: Sms1 and Sms2 As Regulators Of Sm Homeostasis And Receptor-mmentioning

confidence: 94%

“…Alternatively, dihydrosphingosine (sphinganine) or 4-hydroxysphinganine (phytosphingosine) could account for the sphingoid backbone and unsaturated and/or branched fatty acids could also be found. 49,50 Even though structurally similar, SM and phosphatidylcholine (PC) differ significantly for a number of features that determine the higher melting temperature of the first. In fact, the predominant presence of saturated fatty acids and the potential intermolecular hydrogen binding, via the amide bond and the free hydroxyl group at position 3, favor a high-density packing of SM, which increases the compactness and impermeability of the membrane.…”

Section: Physicochemical Properties Of Smmentioning

confidence: 99%

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Tales and Mysteries of the Enigmatic Sphingomyelin Synthase Family

Holthuis

Luberto

2010

Advances in Experimental Medicine and Biology

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In the last five years tremendous progress has been made toward the understanding of the mechanisms that govern sphingomyelin (SM) synthesis in animal cells. In line with the complexity of most biological processes, also in the case of SM biosynthesis, the more we learn the more enigmatic and finely tuned the system appears. Therefore with this review we aim first, at highlighting the most significant discoveries that advanced our knowledge and understanding of SM biosynthesis, starting from the discovery of SM to the identification of the enzymes responsible for its production; and second, at discussing old and new riddles that such discoveries pose to current investigators.

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Section: Sms1 and Sms2 As Regulators Of Sm Homeostasis And Receptor-mmentioning

confidence: 94%

Section: Physicochemical Properties Of Smmentioning

confidence: 99%

Tales and Mysteries of the Enigmatic Sphingomyelin Synthase Family

Holthuis

Luberto

2010

Advances in Experimental Medicine and Biology

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“…The methods for sphingolipid analysis have been described in depth previously (43). Briefly, to each collected adipocyte sample in a glass test tube 0.5 ml of methanol, 0.25 ml of chloroform, and the internal standards were added.…”

Section: Sphingolipid Analysismentioning

confidence: 99%

Aging Up-Regulates Expression of Inflammatory Mediators in Mouse Adipose Tissue

Ren

Pae

et al. 2007

The Journal of Immunology

255

209

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The incidence of type 2 diabetes (T2D) increases with age. Low‐grade inflammation in AT is implicated in development of insulin resistance and T2D. We conducted a study to determine if inflammatory responses are upregulated with age in AT. Results show that visceral AT from old mice had significantly higher expression of mRNA levels of IL‐1β, IL‐6, TNF‐α, and COX‐2 than those of young mice (263, 208, 165, and 73%, higher respectively). In determining the relative contribution of different components of AT to these age‐related changes, we found that adipocytes (AD) from old mice produced significantly more (2 to 3 folds) IL‐6 and PGE2 than those from young mice while no significant age difference was observed in their production by stromal vascular cells. There was no significant effect of age on number of Mϕ/g AT and Mϕ of either age group produced significantly more IL‐6 when incubated in conditioned medium from old AD compared to that of young. Blocking NF‐κB activation reduced IL‐6 production while addition of ceramide or sphingomyelinase increased IL‐6 production in young AD to a level comparable to that of old AD. Inhibiting de novo ceramide synthesis reduced IL‐6 production by AD. NF‐κB regulates expression of inflammatory products including COX‐2 and IL‐6. Ceramide was shown to increase COX‐2 expression in aged Mϕ through NF‐κB activation. Thus, these data suggest a potential role for ceramide and NF‐κB in the age‐related increase of AT inflammation. Further research is needed to fully determine the underlying mechanisms of the observed effects and their contribution to T2D in the aged. Supported by USDA #58‐1950‐9‐001 and NIA #R01 AG009140‐10A1.

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“…To this end, analysis of sphingolipids by shotgun lipidomics is challenging due to the hundreds of molecular species present, with many present in diminutive amounts. The majority of established methods for the large-scale analysis of sphingolipids are developed based on LC and LC-MS [24][25][26][27][28][29][30].…”

Section: Nih Public Accessmentioning

confidence: 99%

Alkaline methanolysis of lipid extracts extends shotgun lipidomics analyses to the low-abundance regime of cellular sphingolipids

Jiang

Cheng

Yang

et al. 2007

Analytical Biochemistry

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Sphingolipids that contain a sphingoid base are composed of hundreds to thousands of distinct compounds, many of which serve as lipid regulators of biological functions. The global analysis of the large number of low-abundance sphingolipid molecular species has been hampered in many cases by the sphingolipid molecular species being overwhelmed by the quantity of other classes of lipid (e.g., glycerophospholipid) molecular species present, thereby imposing severe restrictions on the dynamic range of their measurement using shotgun lipidomics. Herein, we developed a facile approach in which the sphingolipids of cellular extracts were dramatically enriched by direct alkaline methanolysis of lipid extracts followed by extraction to remove the large majority of other endogenous lipid classes. Through direct infusion of the resultant enriched solution, we identified and quantitated a variety of very-low-abundance sphingolipid classes (e.g., sphingosine, psychosine, and lysosphingomyelin) and molecular species (e.g., sphingomyelin) using electrospray ionization mass spectrometry (i.e., shotgun sphingolipidomics). Accordingly, through utilization of these facile enrichment techniques, direct penetrance into the sphingolipidomes has been greatly extended, facilitating new insights into their metabolism and signaling functions in biological systems. KeywordsElectrospray ionization mass spectrometry; Shotgun lipidomics; Shotgun sphingolipidomics; Sphingolipidome; Lysosphingomyelin; Psychosine; Sphingomyelin; Sphingosine Lipidomics, the large-scale study of the pathways and networks of cellular lipids, is an emerging and rapidly expanding research field [1][2][3]. Currently, lipidomics research has been focused on identifying alterations in lipid metabolic pathways and networks induced by a disease state, a gene mutation (knockout or overexpression), a therapeutic treatment, or other perturbations. In the future, research in lipidomics will expand to include the dynamics of lipidomes, subcellular organizations of lipidomes, and interactions of lipids with lipids, proteins, and other cellular moieties. Although lipidomics has emerged as a distinct field only within the past few years [1][2][3], numerous new discoveries and/or advances have already been made [3][4][5][6][7][8][9][10][11][12]. Its essential roles in identifying the biochemical mechanisms of lipid metabolism, investigating the functions of an individual gene of interest, identifying novel biomarkers, and evaluating drug efficacy, among others, are becoming increasingly recognized.One of the major analytical platforms in current lipidomics practice is multidimensional massspectrometry (MS) 1 -based shotgun lipidomics [13][14][15]. This platform has now evolved into a mature technology that includes a series of simple steps such as multiplexed extractions, *Corresponding author. Fax: +1 314 362 1402. E-mail address: xianlin@wustl.edu (X. Han).. intrasource separation, identification of individual lipid molecular species using multidimensional MS, and quan...

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Sphingolipidomics: High-throughput, structure-specific, and quantitative analysis of sphingolipids by liquid chromatography tandem mass spectrometry

Cited by 549 publications

References 25 publications

Tales and Mysteries of the Enigmatic Sphingomyelin Synthase Family

Tales and Mysteries of the Enigmatic Sphingomyelin Synthase Family

Aging Up-Regulates Expression of Inflammatory Mediators in Mouse Adipose Tissue

Alkaline methanolysis of lipid extracts extends shotgun lipidomics analyses to the low-abundance regime of cellular sphingolipids

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