Advertisement

Analytical and Bioanalytical Chemistry

, Volume 407, Issue 17, pp 5199–5210 | Cite as

Multidimensional mass spectrometry-based shotgun lipidomics analysis of vinyl ether diglycerides

  • Kui Yang
  • Christopher M. Jenkins
  • Beverly Dilthey
  • Richard W. GrossEmail author
Research Paper
Part of the following topical collections:
  1. Lipidomics

Abstract

Diglycerides play a central role in lipid metabolism and signaling in mammalian cells. Although diacylglycerol molecular species comprise the majority of cellular diglycerides that are commonly measured using a variety of approaches, identification of extremely low abundance vinyl ether diglycerides has remained challenging. In this work, representative molecular species from the three diglyceride subclasses (diacyl, vinyl ether, and alkyl ether diglycerides; hereafter referred to as diradylglycerols) were interrogated by mass spectrometric analysis. Product ion mass spectra of the synthesized diradylglycerols with varied chain lengths and degrees of unsaturation demonstrated diagnostic fragmentation patterns indicative of each subclass. Multidimensional mass spectrometry-based shotgun lipidomics (MDMS-SL) analysis of mouse brain and heart lipid extracts were performed using the identified informative signature product ions. Through an array of tandem mass spectrometric analyses utilizing the orthogonal characteristics of neutral loss scanning and precursor ion scanning, the differential fragmentation of each subclass was exploited for high-yield structural analyses. Although molecular ion mass spectra readily identified diacylglycerol molecular species directly from the hexane fractions of tissue extracts enriched in nonpolar lipids, molecular ion peaks corresponding to ether-linked diglycerides were not observable. The power of MDMS-SL utilizing the tandem mass spectrometric array analysis was demonstrated by identification and profiling of individual molecular species of vinyl ether diglycerides in mouse brain and heart from their undetectable molecular ion peaks during MS1 analysis. Collectively, this technology enabled the identification and profiling of previously inaccessible vinyl ether diglyceride molecular species in mammalian tissues directly from extracts of biologic tissues.

Graphical Abstract

Keywords

Plasmalogen Vinyl ether Vinyl ether diglycerides Shotgun lipidomics 

Notes

Acknowledgments

This work was supported, in whole or in part, by National Institutes of Health Grants RO1HL118639-02 and RO1DK100679-01A1. R. W. G. has financial relationships with LipoSpectrum and Platomics.

Supplementary material

216_2015_8640_MOESM1_ESM.pdf (1.5 mb)
ESM 1 (PDF 1571 kb)

References

  1. 1.
    Leonard TA, Hurley JH (2011) Regulation of protein kinases by lipids. Curr Opin Struct Biol 21(6):785–791. doi: 10.1016/j.sbi.2011.07.006 CrossRefGoogle Scholar
  2. 2.
    Makide K, Kitamura H, Sato Y, Okutani M, Aoki J (2009) Emerging lysophospholipid mediators, lysophosphatidylserine, lysophosphatidylthreonine, lysophosphatidylethanolamine and lysophosphatidylglycerol. Prostaglandins Lipid Mediat 89(3–4):135–139. doi: 10.1016/j.prostaglandins.2009.04.009 CrossRefGoogle Scholar
  3. 3.
    Nakamura MT, Yudell BE, Loor JJ (2014) Regulation of energy metabolism by long-chain fatty acids. Prog Lipid Res 53:124–144. doi: 10.1016/j.plipres.2013.12.001 CrossRefGoogle Scholar
  4. 4.
    Poveda JA, Giudici AM, Renart ML, Molina ML, Montoya E, Fernandez-Carvajal A, Fernandez-Ballester G, Encinar JA, Gonzalez-Ros JM (2014) Lipid modulation of ion channels through specific binding sites. Biochim Biophys Acta 1838(6):1560–1567. doi: 10.1016/j.bbamem.2013.10.023 CrossRefGoogle Scholar
  5. 5.
    Rolim AE, Henrique-Araujo R, Ferraz EG, de Araujo Alves Dultra FK, Fernandez LG (2014) Lipidomics in the study of lipid metabolism: current perspectives in the omic sciences. Gene 554(2):131–139. doi: 10.1016/j.gene.2014.10.039 CrossRefGoogle Scholar
  6. 6.
    Brugger B (2014) Lipidomics: analysis of the lipid composition of cells and subcellular organelles by electrospray ionization mass spectrometry. Annu Rev Biochem 83:79–98. doi: 10.1146/annurev-biochem-060713-035324 CrossRefGoogle Scholar
  7. 7.
    Ecker J, Liebisch G (2014) Application of stable isotopes to investigate the metabolism of fatty acids, glycerophospholipid and sphingolipid species. Prog Lipid Res 54:14–31. doi: 10.1016/j.plipres.2014.01.002 CrossRefGoogle Scholar
  8. 8.
    Junot C, Fenaille F, Colsch B, Becher F (2014) High resolution mass spectrometry based techniques at the crossroads of metabolic pathways. Mass Spectrom Rev 33(6):471–500. doi: 10.1002/mas.21401 CrossRefGoogle Scholar
  9. 9.
    Han X, Yang K, Gross RW (2012) Multi-dimensional mass spectrometry-based shotgun lipidomics and novel strategies for lipidomic analyses. Mass Spectrom Rev 31(1):134–178. doi: 10.1002/mas.20342 CrossRefGoogle Scholar
  10. 10.
    Gross RW, Holcapek M (2014) Lipidomics Anal Chem 86(17):8Google Scholar
  11. 11.
    Ford DA, Miyake R, Glaser PE, Gross RW (1989) Activation of protein kinase C by naturally occurring ether-linked diglycerides. J Biol Chem 264(23):13818–13824Google Scholar
  12. 12.
    Ford DA, Gross RW (1990) Activation of myocardial protein kinase C by plasmalogenic diglycerides. Am J Physiol 258(1 Pt 1):C30–C36Google Scholar
  13. 13.
    Ford DA, Rosenbloom KB, Gross RW (1992) The primary determinant of rabbit myocardial ethanolamine phosphotransferase substrate selectivity is the covalent nature of the sn-1 aliphatic group of diradyl glycerol acceptors. J Biol Chem 267(16):11222–11228Google Scholar
  14. 14.
    Murphy RC, James PF, McAnoy AM, Krank J, Duchoslav E, Barkley RM (2007) Detection of the abundance of diacylglycerol and triacylglycerol molecular species in cells using neutral loss mass spectrometry. Anal Biochem 366(1):59–70CrossRefGoogle Scholar
  15. 15.
    Blachnio-Zabielska AU, Zabielski P, Jensen MD (2013) Intramyocellular diacylglycerol concentrations and [U-(1)(3)C]palmitate isotopic enrichment measured by LC/MS/MS. J Lipid Res 54(6):1705–1711CrossRefGoogle Scholar
  16. 16.
    Mu H, Sillen H, Hiy C-E (2000) Identification of diacylglycerols and triacylglycerols in a structured lipid sample by atmospheric pressure chemical ionization liquid chromatography/mass spectrometry. J Am Oil Chem Soc 77(10):1049–1060. doi: 10.1007/s11746-000-0166-6 CrossRefGoogle Scholar
  17. 17.
    Wang M, Hayakawa J, Yang K, Han X (2014) Characterization and quantification of diacylglycerol species in biological extracts after one-step derivatization: a shotgun lipidomics approach. Anal Chem 86(4):2146–2155CrossRefGoogle Scholar
  18. 18.
    Callender HL, Forrester JS, Ivanova P, Preininger A, Milne S, Brown HA (2007) Quantification of diacylglycerol species from cellular extracts by electrospray ionization mass spectrometry using a linear regression algorithm. Anal Chem 79(1):263–272CrossRefGoogle Scholar
  19. 19.
    Haag M, Schmidt A, Sachsenheimer T, Brugger B (2012) Quantification of signaling lipids by nano-electrospray ionization tandem mass spectrometry (nano-ESI MS/MS). Metabolites 2(1):57–76CrossRefGoogle Scholar
  20. 20.
    Han X, Gross RW (2005) Shotgun lipidomics: multidimensional MS analysis of cellular lipidomes. Expert Rev Proteomics 2(2):253–264CrossRefGoogle Scholar
  21. 21.
    Yang K, Cheng H, Gross RW, Han X (2009) Automated lipid identification and quantification by multidimensional mass spectrometry-based shotgun lipidomics. Anal Chem 81(11):4356–4368CrossRefGoogle Scholar
  22. 22.
    Han X, Yang K, Gross RW (2012) Multi-dimensional mass spectrometry-based shotgun lipidomics and novel strategies for lipidomic analyses. Mass Spectrom Rev 31(1):134–178CrossRefGoogle Scholar
  23. 23.
    Gross RW, Han X (2011) Lipidomics at the interface of structure and function in systems biology. Chem Biol 18(3):284–291CrossRefGoogle Scholar
  24. 24.
    Han X, Gross RW (2003) Global analyses of cellular lipidomes directly from crude extracts of biological samples by ESI mass spectrometry: a bridge to lipidomics. J Lipid Res 44(6):1071–1079CrossRefGoogle Scholar
  25. 25.
    Han X, Gross RW (1995) Structural determination of picomole amounts of phospholipids via electrospray ionization tandem mass spectrometry. J Am Soc Mass Spectrom 6(12):1202–1210CrossRefGoogle Scholar
  26. 26.
    Han X, Gross RW (1994) Electrospray ionization mass spectroscopic analysis of human erythrocyte plasma membrane phospholipids. Proc Natl Acad Sci U S A 91(22):10635–10639CrossRefGoogle Scholar
  27. 27.
    Hara A, Radin NS (1978) Lipid extraction of tissues with a low-toxicity solvent. Anal Biochem 90(1):420–426CrossRefGoogle Scholar
  28. 28.
    Wittenberg JB, Korey SR, Swenson FH (1956) The determination of higher fatty aldehydes in tissues. J Biol Chem 219(1):39–47Google Scholar
  29. 29.
    Han X, Yang K, Gross RW (2008) Microfluidics-based electrospray ionization enhances the intrasource separation of lipid classes and extends identification of individual molecular species through multi-dimensional mass spectrometry: development of an automated high-throughput platform for shotgun lipidomics. Rapid Commun Mass Spectrom 22(13):2115–2124CrossRefGoogle Scholar
  30. 30.
    Gross RW, Jenkins CM, Yang J, Mancuso DJ, Han X (2005) Functional lipidomics: the roles of specialized lipids and lipid-protein interactions in modulating neuronal function. Prostaglandins Lipid Mediat 77(1–4):52–64. doi: 10.1016/j.prostaglandins.2004.09.005 CrossRefGoogle Scholar
  31. 31.
    Farooqui AA, Horrocks LA, Farooqui T (2000) Glycerophospholipids in brain: their metabolism, incorporation into membranes, functions, and involvement in neurological disorders. Chem Phys Lipids 106(1):1–29CrossRefGoogle Scholar
  32. 32.
    Sastry PS (1985) Lipids of nervous tissue: composition and metabolism. Prog Lipid Res 24(2):69–176CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Kui Yang
    • 1
  • Christopher M. Jenkins
    • 1
  • Beverly Dilthey
    • 1
  • Richard W. Gross
    • 1
    • 2
    Email author
  1. 1.Division of Bioorganic Chemistry and Molecular Pharmacology, Department of MedicineWashington University School of MedicineSt. LouisUSA
  2. 2.Department of ChemistryWashington UniversitySt. LouisUSA

Personalised recommendations