PMID: PMC3975653-1-4

 

    Legend: Gene, Sites

Title : HDL GangliosidesCharacterized by MS/MS

Abstract :
  1. Gangliosidesare another contributor of sialic acid in HDL
  2. We applied a high resolutionquadrupole time of flight mass spectrometry (Q-TOF MS) method withreverse-phase nanoHPLC separation for the analysis of human HDL gangliosides
  3. The high mass accuracy of these instruments, along with the MS/MScapability, made it possible to perform focused detection of gangliosidespecies in the polar lipid extract
  4. Postprocessingprecursor ion scans indicate the existence of gangliosides, whichelute at certain retention times
  5. Moreover, based on accurate mass,glycan information and ceramide com position were simultaneously obtained
  6. Figure 5 is representative of the ECCs of HDL gangliosides
  7. The chromatogram reveals an elution pattern startingwith gangliosides with shorter ceramide chains followed by those withlonger ceramides
  8. Examination of the profiles shows that GM3 (monosialoganglioside,NeuAc2–3Gal1–4Glc–Cer) and GD3 (disialoganglioside,NeuAc2–8NeuAc2–3Gal1–4Glc–Cer) were abundantganglioside ions in HDL from healthy human plasma, in agreement withearlier studies
  9. Eight GM3 and four GD3gangliosides were detected
  10. A 60% GM3 and 40% GD3 distribution wasobserved, and ion intensities were measured in the MS mode based onthe deprotonated molecular ion (Table 3)
  11. Interestingly,the com position of human aorta from patients who had died of myocardialinfarction were found to have higher GD3 content in the aortic mediaversus the intima, and total gangliosidecontent was found to be lower in cells isolated from atheroscleroticcompared with normal human aorta
  12. Gangliosideshave even been found to stimulate lipoxygenase-mediated eicosanoidproduction in peripheral blood lymphocytes, and GD3 was more stimulatorycompared with GM1 or GM3
  13. These previousreports suggest that ganglioside content and com position may haveimportant biological implications in heart disease and its relatedmechanisms involving lipoproteins
  14. The analysis also revealed the com position of themajor ceramideportion of GM3 and GD3 gangliosides
  15. Both GM3 and GD3 were composedof heterogeneous ceramide lipid tails , including d18:1/16:0 and d18:1/23:0
  16. Types of sphingoid bases and fatty acids in the backbones were determinedwith the use of 80 V MS/MS
  17. Fragments at m/z 264.269 and at m/z 236.238indicated the existence of sphingoid bases d18:1 and d16:1, respectively
  18. As an example, GM3 (d18:1/16:0) yields a diagnostic sialic acid fragmentat m/z 290.09 in 40 V negative modeMS/MS, while 80 V positive mode MS/MS spectrum provides the ceramideinformation at m/z 520.49 and 264.27(Supplemental Figure S2, Supporting Information)
  19. The importance of the ceramide lipid tail com position al differencesis currently poorly understood
  20. For example, transmembrane anchoredangiotensin converting enzyme , an enzyme important for blood pressureregulation, was found to associate only with C18 but not C16 sphingomyelin-containingrafts
  21. A recent report showed that nascent HDL resemble lipid rafts, suggesting the possibility that HDL particleshave micro-heterogeneity with lipid raftlike portions of the phospholipidouter layer that recruit specific gangliosides and proteins to performspecific functions, just as occurs in plasma membrane lipid rafts
  22. The simultaneous identification of the glycanand ceramide will provide a clearer picture of the role of gangliosidesin lipoprotein biology
Output (sent_index, trigger, protein, sugar, site):
  • 1. acid, , HDL, acid, -
Output(Part-Of) (sent_index, protein, site):
*Output_Site_Fusion* (sent_index, protein, sugar, site):

 

 

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