Skip to main content

Advanced Shotgun Lipidomics for Characterization of Altered Lipid Patterns in Neurodegenerative Diseases and Brain Injury

  • Protocol
Systems Biology of Alzheimer's Disease

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1303))

Abstract

Multi-dimensional mass spectrometry-based shotgun lipidomics (MDMS-SL) is a powerful technology platform among current lipidomics practices due to its high efficiency, sensitivity, and reproducibility, as well as its broad coverage. This platform has been widely used to determine the altered lipid profiles induced by diseases, injury, genetic manipulations, drug treatments, and aging, among others. Herein, we summarize the principles underlying this platform and present a protocol for analysis of many of the lipid classes and subclasses covered by MDMS-SL directly from lipid extracts of brain samples. We believe that this protocol can aid researchers in the field to determine altered lipid patterns in neurodegenerative diseases and brain injury.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 249.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. 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 44:1071–1079

    Article  CAS  PubMed  Google Scholar 

  2. Lagarde M, Geloen A, Record M et al (2003) Lipidomics is emerging. Biochim Biophys Acta 1634:61

    Article  CAS  PubMed  Google Scholar 

  3. Wenk MR (2005) The emerging field of lipidomics. Nat Rev Drug Discov 4:594–610

    Article  CAS  PubMed  Google Scholar 

  4. Han X, Gross RW (2005) Shotgun lipidomics: electrospray ionization mass spectrometric analysis and quantitation of the cellular lipidomes directly from crude extracts of biological samples. Mass Spectrom Rev 24:367–412

    Article  CAS  PubMed  Google Scholar 

  5. Walker JM, Krey JF, Chen JS et al (2005) Targeted lipidomics: fatty acid amides and pain modulation. Prostaglandins Other Lipid Mediat 77:35–45

    Article  CAS  PubMed  Google Scholar 

  6. Serhan CN (2005) Mediator lipidomics. Prostaglandins Other Lipid Mediat 77:4–14

    Article  CAS  PubMed  Google Scholar 

  7. Han X (2007) Neurolipidomics: challenges and developments. Front Biosci 12:2601–2615

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  8. Ivanova PT, Milne SB, Forrester JS, Brown HA (2004) LIPID arrays: new tools in the understanding of membrane dynamics and lipid signaling. Mol Interv 4:86–96

    Article  CAS  PubMed  Google Scholar 

  9. Welti R, Shah J, Li W et al (2007) Plant lipidomics: discerning biological function by profiling plant complex lipids using mass spectrometry. Front Biosci 12:2494–2506

    Article  CAS  PubMed  Google Scholar 

  10. Schiller J, Suss R, Fuchs B et al (2007) MALDI-TOF MS in lipidomics. Front Biosci 12:2568–2579

    Article  CAS  PubMed  Google Scholar 

  11. Albert CJ, Anbukumar DS, Monda JK et al (2007) Myocardial lipidomics. Developments in myocardial nuclear lipidomics. Front Biosci 12:2750–2760

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  12. Ejsing CS, Duchoslav E, Sampaio J et al (2006) Automated identification and quantification of glycerophospholipid molecular species by multiple precursor ion scanning. Anal Chem 78:6202–6214

    Article  CAS  PubMed  Google Scholar 

  13. Han X, Gross RW (2005) Shotgun lipidomics: multi-dimensional mass spectrometric analysis of cellular lipidomes. Expert Rev Proteomics 2:253–264

    Article  CAS  PubMed  Google Scholar 

  14. Han X, Yang K, Gross RW (2012) Multi-dimensional mass spectrometry-based shotgun lipidomics and novel strategies for lipidomic analyses. Mass Spectrom Rev 31:134–178

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  15. Tsui ZC, Chen QR, Thomas MJ et al (2005) A method for profiling gangliosides in animal tissues using electrospray ionization-tandem mass spectrometry. Anal Biochem 341:251–258

    Article  CAS  PubMed  Google Scholar 

  16. Kalderon B, Sheena V, Shachrur S et al (2002) Modulation by nutrients and drugs of liver acyl-CoAs analyzed by mass spectrometry. J Lipid Res 43:1125–1132

    Article  CAS  PubMed  Google Scholar 

  17. Golovko MY, Murphy EJ (2004) An improved method for tissue long-chain acyl-CoA extraction and analysis. J Lipid Res 45:1777–1782

    Article  CAS  PubMed  Google Scholar 

  18. Han X, Yang K, Cheng H et al (2005) Shotgun lipidomics of phosphoethanolamine-containing lipids in biological samples after one-step in situ derivatization. J Lipid Res 46:1548–1560

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  19. Jiang X, Cheng H, Yang K et al (2007) Alkaline methanolysis of lipid extracts extends shotgun lipidomics analyses to the low abundance regime of cellular sphingolipids. Anal Biochem 371:135–145

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  20. Yang K, Zhao Z, Gross RW, Han X (2007) Shotgun lipidomics identifies a paired rule for the presence of isomeric ether phospholipid molecular species. PLoS One 2:e1368

    Article  PubMed Central  PubMed  Google Scholar 

  21. Ikonomou MG, Blades AT, Kebarle P (1991) Electrospray-ion spray: a comparison of mechanisms and performance. Anal Chem 63:1989–1998

    Article  CAS  Google Scholar 

  22. Gaskell SJ (1997) Electrospray: principles and practice. J Mass Spectrom 32:677–688

    Article  CAS  Google Scholar 

  23. Han X, Yang J, Cheng H et al (2004) Towards fingerprinting cellular lipidomes directly from biological samples by two-dimensional electrospray ionization mass spectrometry. Anal Biochem 330:317–331

    Article  CAS  PubMed  Google Scholar 

  24. Han X, Yang K, Yang J et al (2006) Factors influencing the electrospray intrasource separation and selective ionization of glycerophospholipids. J Am Soc Mass Spectrom 17:264–274

    Article  CAS  PubMed  Google Scholar 

  25. Han X, Cheng H, Mancuso DJ, Gross RW (2004) Caloric restriction results in phospholipid depletion, membrane remodeling and triacylglycerol accumulation in murine myocardium. Biochemistry 43:15584–15594

    Article  CAS  PubMed  Google Scholar 

  26. Schwudke D, Oegema J, Burton L et al (2006) Lipid profiling by multiple precursor and neutral loss scanning driven by the data-dependent acquisition. Anal Chem 78:585–595

    Article  CAS  PubMed  Google Scholar 

  27. Han X, Gross RW (2001) Quantitative analysis and molecular species fingerprinting of triacylglyceride molecular species directly from lipid extracts of biological samples by electrospray ionization tandem mass spectrometry. Anal Biochem 295:88–100

    Article  CAS  PubMed  Google Scholar 

  28. Han X, Gross RW (1995) Structural determination of picomole amounts of phospholipids via electrospray ionization tandem mass spectrometry. J Am Soc Mass Spectrom 6:1202–1210

    Article  CAS  PubMed  Google Scholar 

  29. Brugger B, Erben G, Sandhoff R et al (1997) Quantitative analysis of biological membrane lipids at the low picomole level by nano-electrospray ionization tandem mass spectrometry. Proc Natl Acad Sci U S A 94:2339–2344

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  30. Lehmann WD, Koester M, Erben G, Keppler D (1997) Characterization and quantification of rat bile phosphatidylcholine by electrospray-tandem mass spectrometry. Anal Biochem 246:102–110

    Article  CAS  PubMed  Google Scholar 

  31. Welti R, Li W, Li M et al (2002) Profiling membrane lipids in plant stress responses. Role of phospholipase Da in freezing-induced lipid changes in Arabidopsis. J Biol Chem 277:31994–32002

    Article  CAS  PubMed  Google Scholar 

  32. Welti R, Wang X (2004) Lipid species profiling: a high-throughput approach to identify lipid compositional changes and determine the function of genes involved in lipid metabolism and signaling. Curr Opin Plant Biol 7:337–344

    Article  CAS  PubMed  Google Scholar 

  33. Han X, Yang K, Yang J et al (2006) Shotgun lipidomics of cardiolipin molecular species in lipid extracts of biological samples. J Lipid Res 47:864–879

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  34. Wang M, Fang H, Han X (2012) Shotgun lipidomics analysis of 4-hydroxyalkenal species directly from lipid extracts after one-step in situ derivatization. Anal Chem 84:4580–4586

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  35. Jiang X, Han X (2006) Characterization and direct quantitation of sphingoid base-1-phosphates from lipid extracts: a shotgun lipidomics approach. J Lipid Res 47:1865–1873

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  36. Cheng H, Sun G, Yang K et al (2010) Selective desorption/ionization of sulfatides by MALDI-MS facilitated using 9-aminoacridine as matrix. J Lipid Res 51:1599–1609

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  37. Han X, Holtzman DM, McKeel DW Jr (2001) Plasmalogen deficiency in early Alzheimer's disease subjects and in animal models: molecular characterization using electrospray ionization mass spectrometry. J Neurochem 77:1168–1180

    Article  CAS  PubMed  Google Scholar 

  38. Christie WW, Han X (2010) Lipid analysis: isolation, separation, identification and lipidomic analysis, 4th edn. The Oily Press, Bridgwater, UK

    Book  Google Scholar 

  39. Cheng H, Wang M, Li J-L et al (2013) Specific changes of sulfatide levels in individuals with pre-clinical Alzheimer’s disease: an early event in disease pathogenesis. J Neurochem 127:733–738

    Article  CAS  PubMed  Google Scholar 

  40. Yang K, Cheng H, Gross RW, Han X (2009) Automated lipid identification and quantification by multi-dimensional mass spectrometry-based shotgun lipidomics. Anal Chem 81:4356–4368

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  41. Yang K, Fang X, Gross RW, Han X (2011) A practical approach for determination of mass spectral baselines. J Am Soc Mass Spectrom 22:2090–2099

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  42. Vance DE, Vance JE (2008) Biochemistry of lipids, lipoproteins and membranes, 5th edn. Elsevier Science B.V., Amsterdam, The Netherlands

    Google Scholar 

  43. Yang K, Zhao Z, Gross RW, Han X (2009) Systematic analysis of choline-containing phospholipids using multi-dimensional mass spectrometry-based shotgun lipidomics. J Chromatogr B 877:2924–2936

    Article  CAS  Google Scholar 

  44. Han X (2002) Characterization and direct quantitation of ceramide molecular species from lipid extracts of biological samples by electrospray ionization tandem mass spectrometry. Anal Biochem 302:199–212

    Article  CAS  PubMed  Google Scholar 

  45. Han X, Cheng H (2005) Characterization and direct quantitation of cerebroside molecular species from lipid extracts by shotgun lipidomics. J Lipid Res 46:163–175

    Article  CAS  PubMed  Google Scholar 

  46. Hsu FF, Turk J (2001) Structural determination of glycosphingolipids as lithiated adducts by electrospray ionization mass spectrometry using low-energy collisional-activated dissociation on a triple stage quadrupole instrument. J Am Soc Mass Spectrom 12:61–79

    Article  CAS  PubMed  Google Scholar 

  47. Hsu F-F, Bohrer A, Turk J (1998) Electrospray ionization tandem mass spectrometric analysis of sulfatide. Determination of fragmentation patterns and characterization of molecular species expressed in brain and in pancreatic islets. Biochim Biophys Acta 1392:202–216

    Article  CAS  PubMed  Google Scholar 

  48. Jiang X, Yang K, Han X (2009) Direct quantitation of psychosine from alkaline-treated lipid extracts with a semi-synthetic internal standard. J Lipid Res 50:162–172

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  49. Cheng H, Jiang X, Han X (2007) Alterations in lipid homeostasis of mouse dorsal root ganglia induced by apolipoprotein E deficiency: a shotgun lipidomics study. J Neurochem 101:57–76

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  50. Su X, Han X, Mancuso DJ et al (2005) Accumulation of long-chain acylcarnitine and 3-hydroxy acylcarnitine molecular species in diabetic myocardium: identification of alterations in mitochondrial fatty acid processing in diabetic myocardium by shotgun lipidomics. Biochemistry 44:5234–5245

    Article  CAS  PubMed  Google Scholar 

  51. Han X (2010) Multi-dimensional mass spectrometry-based shotgun lipidomics and the altered lipids at the mild cognitive impairment stage of Alzheimer’s disease. Biochim Biophys Acta 1801:774–783

    Article  CAS  PubMed Central  PubMed  Google Scholar 

Download references

Acknowledgements

This work was partially supported by National Institute of General Medical Sciences Grant R01 GM105724 and intramural institutional research funds. Special thanks are expressed to Ms. Imee Tiu for her editorial assistance.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Xianlin Han Ph.D. .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer Science+Business Media New York

About this protocol

Cite this protocol

Wang, M., Han, X. (2016). Advanced Shotgun Lipidomics for Characterization of Altered Lipid Patterns in Neurodegenerative Diseases and Brain Injury. In: Castrillo, J., Oliver, S. (eds) Systems Biology of Alzheimer's Disease. Methods in Molecular Biology, vol 1303. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-2627-5_24

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-2627-5_24

  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-2626-8

  • Online ISBN: 978-1-4939-2627-5

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics