Apprehending ganglioside diversity: a comprehensive methodological approach

Masson, Elodie; Sibille, Estelle; Martine, Lucy; Chaux-Picquet, Fanny; Brétillon, Lionel; Berdeaux, Olivier

doi:10.1194/jlr.d060764

Cited by 24 publications

(29 citation statements)

References 50 publications

(59 reference statements)

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“…The ceramide structures (combinations of LCB and FA) were determined after fragmentation of the GG molecular species using the LTQ-Orbitrap mass spectrometer, as detailed previously [1]. The LCB were identified and the associated FA was then deduced based on the exact mass of the molecule.…”

Section: Resultsmentioning

confidence: 99%

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Ganglioside Profiling of the Human Retina: Comparison with Other Ocular Structures, Brain and Plasma Reveals Tissue Specificities

et al. 2016

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Gangliosides make a wide family of glycosphingolipids, highly heterogeneous in both the ceramide moiety and the oligosaccharide chain. While ubiquitously expressed in mammalian tissues, they are particularly abundant in the brain and the peripheral nervous system. Gangliosides are known to play a crucial role in the development, maintenance and functional integrity of the nervous system. However, the expression and roles of gangliosides in the retina, although often considered as a window on the brain, has been far less studied. We performed an in-depth analysis of gangliosides of the human retina, especially using powerful LC/MS methods. We compared the pattern of ganglioside classes and ceramide molecular species of this tissue with other ocular structures and with brain and plasma in elderly human individuals. About a hundred of ganglioside molecular species among 15 distinct classes were detected illustrating the huge structural diversity of these compounds. The retina exhibited a very diverse ganglioside profile and shared several common features with the brain (prominence of tetraosylgangliosides, abundance of d20:1 long chain base and 18:0 fatty acid…). However, the retina stood out with the specific expression of GD3, GT3 and AcGT3, which further presented a peculiar molecular species distribution. The unique ganglioside pattern we observed in the human retina suggests that these ganglioside species play a specific role in the structure and function of this tissue. This lipidomic study, by highlighting retina specific ganglioside species, opens up novel research directions for a better understanding of the biological role of gangliosides in the retina.

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Section: Resultsmentioning

confidence: 99%

“…in human brain [36]. Regarding the retina, we previously detected several molecular species of GT3 and AcGT3 in rat samples [1]. Literature data regarding GT3 is very poor.…”

Section: Discussionmentioning

confidence: 99%

Ganglioside Profiling of the Human Retina: Comparison with Other Ocular Structures, Brain and Plasma Reveals Tissue Specificities

et al. 2016

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“…4b). Moreover, the B 1β fragment ( m/z 290.0888) known as Neu5Ac marker 8,13,15,17 is absent in the oxidized species, instead the corresponding m/z 228.0519 was observed ( cf. Fig.…”

Section: Resultsmentioning

confidence: 99%

Isobaric Labeling of Intact Gangliosides toward Multiplexed LC–MS/MS-Based Quantitative Analysis

Barrientos

Zhang²

2018

Anal. Chem.

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Gangliosides are sialic acid-containing glycosphingolipids recognized to play essential role in biological processes. Both the glycan and lipid structures influence their biological function and thus necessitate their determination as intact molecular species. To our knowledge, no multiplexed method for intact gangliosides currently exists. In this paper, we aimed to demonstrate an approach for isobaric labeling of intact gangliosides. Specifically, we carried out the rapid, chemoselective oxidation of sialic acid side chain in common ganglioside core structures using NaIO followed by ligation with a carbonyl-reactive isobaric tandem mass tag (TMT) reagent and subsequent RPLC-MS/MS analysis. Attachment of the isobaric label was observed to improve the ionization efficiency of complex gangliosides using electrospray ionization. Fragmentation of the resulting [M + 2H] ions of TMT-labeled gangliosides provided information-rich spectra containing fragments from the glycan, lipid, and TMT reporter ions. This facile approach enabled simultaneous quantification of up to six samples as well as identification of glycan and lipid compositions in a single injection. As a proof-of-concept, using porcine brain total ganglioside extracts pooled at known ratios, we obtained overall sample-to-sample precision of <12% RSD and mean error of <10%. This showcased the great promise and feasibility of this strategy for high-throughput analysis of intact gangliosides in biological extracts.

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“…GGs were prepared by biphasic extraction as previously described [21]. Briefly, total lipids were first extracted from 1 ml plasma with 10 volumes of chloroform/methanol (1:1, v/v), overnight at 4°C.…”

Section: Methodsmentioning

confidence: 99%

“…GGs were separated by LC and analyzed by MS using both a triple quadrupole mass spectrometer and a high-resolution LTQ Orbitrap mass spectrometer according to previously published methods [21]. …”

Section: Methodsmentioning

confidence: 99%

Plasmatic Ganglioside Profile and Age-Related Macular Degeneration: A Case-Control Study

Dossarps¹,

Martine²,

Berdeaux³

et al. 2016

Ophthalmic Res

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Purpose: Gangliosides are glycosphingolipids that are particularly abundant in the nervous system, including the retina. However, their precise role in this tissue and its pathologies remain poorly understood. The objective of the present study was to characterize the ganglioside profile of human plasma and to determine whether it is affected in age-related macular degeneration (AMD). Methods: Eighty-three subjects were included: control subjects (n = 25), atrophic AMD patients (n = 27) and exudative AMD patients (n = 31). For each subject, gangliosides were extracted from plasma and analyzed by liquid chromatography coupled to mass spectrometry. Results: GM3 appeared to be by far the major ganglioside of human plasma, associated with GD3. No specific ganglioside class was detected in the plasma of AMD patients. Fourteen molecular species of GM3 and 9 species of GD3, accounting for the variability of the ceramide moiety of the ganglioside molecule, were identified and characterized. Analyses revealed no significant differences in the proportion of these species between control, atrophic and exudative AMD patient groups. Total GM3 levels did not differ either. Conclusion: Although gangliosides are considered important for the retina's structure and function, it seems that circulating gangliosides are not associated with the retinal damage occurring during the course of AMD.

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Apprehending ganglioside diversity: a comprehensive methodological approach

Cited by 24 publications

References 50 publications

Ganglioside Profiling of the Human Retina: Comparison with Other Ocular Structures, Brain and Plasma Reveals Tissue Specificities

Ganglioside Profiling of the Human Retina: Comparison with Other Ocular Structures, Brain and Plasma Reveals Tissue Specificities

Isobaric Labeling of Intact Gangliosides toward Multiplexed LC–MS/MS-Based Quantitative Analysis

Plasmatic Ganglioside Profile and Age-Related Macular Degeneration: A Case-Control Study

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