Ionization and fragmentation of neutral and acidic glycosphingolipids with a Q-TOF mass spectrometer fitted with a MALDI ion source

Hunnam, Victoria; Harvey, David J.; Priestman, David A.; Bateman, Robert; Bordoli, Robert S.; Tyldesley, Richard

doi:10.1016/s1044-0305(01)00309-9

Cited by 50 publications

(36 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The samples were dried down in a SpeedVac and resuspended in 20 l of MeOH. Matrix-assisted laser desorption ionization-mass spectrometry was performed as described previously (34).…”

Section: Figmentioning

confidence: 99%

See 1 more Smart Citation

Accumulation of Glycosphingolipids in Niemann-Pick C Disease Disrupts Endosomal Transport

Vruchte

Lloyd-Evans

Veldman

et al. 2004

Journal of Biological Chemistry

172

138

View full text Add to dashboard Cite

Glycosphingolipids are endocytosed and targeted to the Golgi apparatus but are mistargeted to lysosomes in sphingolipid storage disorders. Substrate reduction therapy utilizes imino sugars to inhibit glucosylceramide synthase and potentially abrogate the effects of storage. Niemann-Pick type C (NPC) disease is a disorder of intracellular transport where glycosphingolipids (GSLs) and cholesterol accumulate in endosomal compartments. The mechanisms of altered intracellular trafficking are not known but may involve the mistargeting and disrupted function of proteins associated with GSL membrane microdomains. Membrane microdomains were isolated by Triton X-100 and sucrose density gradient ultracentrifugation. High pressure liquid chromatography and mass spectrometric analysis of NPC1 ؊/؊ mouse brain revealed large increases in GSL. Sphingosine was also found to be a component of membrane microdomains, and in NPC liver and spleen, large increases in cholesterol and sphingosine were found. GSL and cholesterol levels were increased in mutant NPC1-null Chinese hamster ovary cells as well as U18666A and progesterone induced NPC cell culture models. However, inhibition of GSL synthesis in NPC cells with N-butyldeoxygalactonojirimycin led to marked decreases in GSL but only small decreases in cholesterol levels. Both annexin 2 and 6, membrane-associated proteins that are important in endocytic trafficking, show distorted distributions in NPC cells. Altered BODIPY lactosylceramide targeting, decreased endocytic uptake of a fluid phase marker, and mistargeting of annexin 2 (phenotypes associated with NPC) are reversed by inhibition of GSL synthesis. It is suggested that accumulating GSL is part of a mislocalized membrane microdomain and is responsible for the deficit in endocytic trafficking found in NPC disease.Increasing evidence suggests that the membranes of eukaryotic cells are not homogeneously fluid. They contain membrane microdomains, often referred to as lipid rafts and/or caveolae, enriched in glycosphingolipids (GSLs), 1 specific proteins, and cholesterol (1-3). Being operationally defined, i.e. by detergent insolubility and low buoyant density, the natural (in situ) existence of such membrane microdomains has been and continues to be controversial (4). However, they have recently been visualized by using electron microscopy as small structures covering as much as 35% of the cell surface (5). Although membrane microdomains on the cell surface tend to be transient (6), relatively stable microdomains have been visualized in the endocytic pathway (7) where they are proposed to play a role in protein and lipid sorting (8). Many GSL storage diseases, including Niemann-Pick type C (NPC), are often characterized by enlarged liver and spleen as well as severe neurodegeneration. In these diseases, cholesterol and GSLs accumulate in the endocytic pathway because of reduced breakdown. Hence, they may be a useful tool for determining the relative importance of GSLs in endocytic transport. Fibroblasts from patients suffering f...

show abstract

“…The samples were dried down in a SpeedVac and resuspended in 20 l of MeOH. Matrix-assisted laser desorption ionization-mass spectrometry was performed as described previously (34).…”

Section: Figmentioning

confidence: 99%

“…Ϫ/Ϫ mice were initially analyzed by matrix-assisted laser desorption ionization-mass spectrometry (34). No large differences in fatty acid composition could be detected between normal and NPC1…”

Section: Npc1mentioning

confidence: 99%

Accumulation of Glycosphingolipids in Niemann-Pick C Disease Disrupts Endosomal Transport

Vruchte

Lloyd-Evans

Veldman

et al. 2004

Journal of Biological Chemistry

172

138

View full text Add to dashboard Cite

show abstract

“…Different combinations of ionization techniques, ion activation, and mass analyzers have been used, including fast atom bombardment (FAB)-MS [10 -12], infrared-laser desorption MS [13,14], matrix-assisted laser desorption/ionization (MALDI)/magnetic sector MS [15][16][17], electrospray ionization (ESI)-MS [18,19], MALDI/time-offlight (TOF)-MS [20 -22], ESI ion-trap MS [23][24][25], MALDI Fourier transform MS [26], ESI-or MALDIbased quadrupole/TOF-MS [27][28][29][30], MALDI/Postsource Decay (PSD) TOF-MS [31][32][33], and, more recently, MALDI-TOF/TOF-MS [34 -38].…”

mentioning

confidence: 99%

Identification of isomeric N-glycan structures by mass spectrometry with 157 nm laser-induced photofragmentation

Devakumar

Mechref

Kang

et al. 2008

J. Am. Soc. Mass Spectrom.

View full text Add to dashboard Cite

Characterization of structural isomers has become increasingly important and extremely challenging in glycobiology. This communication demonstrates the capability of ion-trap mass spectrometry in conjunction with 157 nm photofragmentation to identify different structural isomers of permethylated N-glycans derived from ovalbumin without chromatographic separation. The results are compared with collision-induced dissociation (CID) experiments. Photodissociation generates extensive cross-ring fragment ions as well as diagnostic glycosidic product ions that are not usually observed in CID MS/MS experiments. The detection of these product ions aids in characterizing indigenous glycan isomers. The ion trap facilitates MS n experiments on the diagnostic glycosidic fragments and cross-ring product ions generated through photofragmentation, thus allowing unambiguous assignment of all of the isomeric structures associated with the model glycoprotein used in this study. Photofragmentation is demonstrated to be a powerful technique for the structural characterization of glycans. , and protein regulations and interactions [6], is widely acknowledged [7]. To improve our understanding of these processes, it is important to explore glycan structure-function relationships. However, the detailed characterization of a glycan structure and its attributes remains a difficult task, given the microheterogeneity and diversity of these molecules. Importantly, the discrimination of numerous structural isomers differing in sequence, linkage, position, or branching features remains a challenging frontier of glycobiology.For years, the characterization of glycan structures has almost exclusively been accomplished by tandem mass spectrometry (MS/MS) [1,8,9] because of its high sensitivity and minimum sample requirements relative to nuclear magnetic resonance (NMR). Different combinations of ionization techniques, ion activation, and A glycan ion generally fragments in two ways: (1) glycosidic cleavages resulting from a bond rupture between two adjacent sugar residues and (2) cross-ring cleavages in which any two bonds on the same sugar unit are broken. Cross-ring fragment ions are commonly observed in high-energy collision-induced dissociation (CID) methods as demonstrated in the tandem TOF/TOF approach [34 -38]. A limitation of this technique, however, is its inability to perform multistage tandem mass spectrometry experiments. On the other hand, glycosidic cleavage ions are predominantly observed in low-energy activation methods and are mainly used to derive sequence and limited branching information. Most recently, demonstrated the use of low-energy activation to identify the structural isomers of glycans in complex mixtures with the help of sequential tandem mass spectrometry (MS n ). However, a disadvantage of CID is the decrease in both the degree and efficiency of dissociation with increasing mass and MS n events. Alternatively, other activation techniques have been used for Address reprint requests to Prof. James P.

show abstract

“…Сфинголипиды исследуют методами масс-спектрометрии последние сорок лет [32,33], при этом использовались различные методы ионизации, в том числе МАЛДИ (матрично-активированная лазерная десорбция/ионизация) [34][35][36][37] и ионизационный электроспрей [28][29][30]. Работали также и с различными типами анализаторов: с секторными [39], квадрупольными [28], времяпролётными [34][35][36]38], ионными ловушками [28,40] и масс-спектрометрами ионного циклотронного резонанса с преобразованием Фурье [37].…”

unclassified

“…Работали также и с различными типами анализаторов: с секторными [39], квадрупольными [28], времяпролётными [34][35][36]38], ионными ловушками [28,40] и масс-спектрометрами ионного циклотронного резонанса с преобразованием Фурье [37]. В результате этих исследований было установлено, что масс-спектрометрия является наилучшим методом изучения сфинголипидов, поскольку обладает:…”

unclassified

The potential role for sphingolipids in neuropathogenesis of Alzheimer’s disease

Alessenko¹

2013

BIOMED KHIM

View full text Add to dashboard Cite

The review discusses the functional role of sphingolipids in the pathogenesis of Alzheimer's disease. Certain evidence exist that the imbalance of sphingolipids such as sphingomyelin, ceramide, sphingosine, sphingosine-1-phosphate and galactosylceramide in the brain of animals and humans, in the cerebrospinal fluid and blood plasma of patients with Alzheimer's disease play a crucial role in neuronal function by regulating growth, differentiation and cell death in CNS. Activation of sphingomyelinase, which leads to the accumulation of the proapoptotic agent, ceramide, can be considered as a new mechanism for AD and may be a prerequisite for the treatment of this disease by using drugs that inhibit sphingomyelinase activity. The role of sphingolipids as biomarkers for the diagnosis of the early stage of Alzheimer's disease and monitoring the effectiveness of treatment with new drugs is discussed.

show abstract

Ionization and fragmentation of neutral and acidic glycosphingolipids with a Q-TOF mass spectrometer fitted with a MALDI ion source

Cited by 50 publications

References 34 publications

Accumulation of Glycosphingolipids in Niemann-Pick C Disease Disrupts Endosomal Transport

Accumulation of Glycosphingolipids in Niemann-Pick C Disease Disrupts Endosomal Transport

Identification of isomeric N-glycan structures by mass spectrometry with 157 nm laser-induced photofragmentation

The potential role for sphingolipids in neuropathogenesis of Alzheimer’s disease

Contact Info

Product

Resources

About