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. 2006 Jun 2;8(2):E391–E395. doi: 10.1007/BF02854910

Brain tissue lipidomics: Direct probing using matrix-assisted laser desorption/ionization mass spectrometry

Amina S Woods 1,, Shelley N Jackson 1
PMCID: PMC3231574  PMID: 16796390

Abstract

Lipidomics is the new frontier in biomolecular structural studies. Not only are lipids the main components in membranes that define the contours of the cell and its organelles, but they are also used for storage. Lipids form stable noncovalent complexes with proteins as well as with many drugs. Lipids are a storage depot for drugs and certain types of organic molecules. To study lipid composition and distribution, complex and time-consuming techniques are used. However, recent advances in mass spectrometry, mainly matrix-assisted laser desorption/ionization (MALDI) have made it possible to directly probe tissues to study structural components, as well as for the localization of drugs. Direct tissue imaging is a powerful tool as it gives a more complete and accurate structural picture and can trace and follow where drugs localize in tissue with minimal anatomical disruption and a minimum of manipulations. Hence, we believe that in addition to its accuracy and efficiency, this new approach will lead to a better understanding of physiological processes as well as the pathophysiology of disease.

Keywords: lipids, MALDI, in situ analysis, tissue

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References

  • 1.Fujiwaki T, Yamaguchi S, Sukegawa K, Taketomi T. Application of delayed extraction matrix-assisted laser desorption ionization time-of-flight mass spectrometry for analysis of sphingolipids in tissues from sphingolipidosis patients. J Chromatogr B Biomed Sci Appl. 1999;731:45–52. doi: 10.1016/S0378-4347(99)00190-5. [DOI] [PubMed] [Google Scholar]
  • 2.He X, Chen F, McGovern MM, Schuchman EH. A fluorescence-based, high-throughput sphingomyelin assay for the analysis of Niemann-Pick disease and other disorders of sphingomyelin metabolism. Anal Biochem. 2002;306:115–123. doi: 10.1006/abio.2002.5686. [DOI] [PubMed] [Google Scholar]
  • 3.Han X, Holtzman DM, McKeel DW, Kelley J, Morris JC. Substantial sulfatide deficiency and ceramide elevation in very early Alzheimer's disease: potential role in disease pathogenesis. J Neurochem. 2002;82:809–818. doi: 10.1046/j.1471-4159.2002.00997.x. [DOI] [PubMed] [Google Scholar]
  • 4.Murphy EJ, Schapiro MB, Rapoport SI, Shetty HU. Phospholipid composition and levels are altered in Down syndrome brain. Brain Res. 2000;867:9–18. doi: 10.1016/S0006-8993(00)02205-8. [DOI] [PubMed] [Google Scholar]
  • 5.Woods AS, Moyer SC, Wang H-YJ, Wise RA. Interaction of chlorisondamine with the neuronal nicotinic acetylcholine receptor. J Proteome Res. 2003;2:207–212. doi: 10.1021/pr025578h. [DOI] [PubMed] [Google Scholar]
  • 6.Woods AS, Ugarov M, Egan T, et al. Lipid/peptide/nucleotide separation with MALDI-ion mobility-TOF MS. Anal Chem. 2004;76:2187–2195. doi: 10.1021/ac035376k. [DOI] [PubMed] [Google Scholar]
  • 7.Woods AS. The mighty arginine, the stable quaternary amines, the powerful aromatics, and the aggressive phosphate: their role in the noncovalent minuet. J Proteome Res. 2004;3:478–484. doi: 10.1021/pr034091l. [DOI] [PubMed] [Google Scholar]
  • 8.Suzuki K. Chemistry and metabolism of brain lipids. In: Albers RW, editor. Basic Neurochemistry. Boston, MA: Little, Brown, and Company; 1972. pp. 207–227. [Google Scholar]
  • 9.Joyce S, Woods AS, Yewdell JW, et al. Natural ligand of mouse CD1d1: cellular glycosylphosphatidylinositol. Science. 1998;279:1541–1544. doi: 10.1126/science.279.5356.1541. [DOI] [PubMed] [Google Scholar]
  • 10.Ceppi P, Colombo S, Francolini M, Raimondo F, Borgese N, Masserini M. Two tail-anchored protein variants, differing in transmembrane domain length and intracellular sorting, interact differently with lipids. Proc Natl Acad Sci USA. 2005;102:16269–16274. doi: 10.1073/pnas.0508157102. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 11.Fisar Z. Interactions between tricyclic antidepressants and phospholipid bilayer membranes. Gen Physiol Biophys. 2005;24:161–180. [PubMed] [Google Scholar]
  • 12.Siuzdak G. Mass Spectrometry for Biotechnology. San Diego, CA: Academic Press; 1996. Ion sources and sample introduction; pp. 11–13. [Google Scholar]
  • 13.Harvey DJ. Matrix-assisted laser desorption/ionization mass spectrometry of phospholipids. J Mass Spectrom. 1995;30:1333–1346. doi: 10.1002/jms.1190300918. [DOI] [Google Scholar]
  • 14.Harvey DJ. Matrix-assisted laser desorption/ionization mass spectrometry of sphingo- and glycosphingo-lipids. J Mass Spectrom. 1995;30:1311–1324. doi: 10.1002/jms.1190300916. [DOI] [Google Scholar]
  • 15.Al-Saad KA, Siems WF, Hill HH, Zabrouskov V, Knowles NR. Structural analysis of phosphatidylcholines by post-source decay matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. J Am Soc Mass Spectrom. 2003;14:373–382. doi: 10.1016/S1044-0305(03)00068-0. [DOI] [PubMed] [Google Scholar]
  • 16.Schiller J, Sub R, Arnhold J, et al. Matrix-assisted laser desorption and ionization time-of-flight (MALDI-TOF) mass spectrometry in lipid and phospholipid research. Prog Lipid Res. 2004;43:449–488. doi: 10.1016/j.plipres.2004.08.001. [DOI] [PubMed] [Google Scholar]
  • 17.Estrada R, Yappert MC. Alternative approaches for the detection of various phospholipid classes by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. J Mass Spectrom. 2004;39:412–422. doi: 10.1002/jms.603. [DOI] [PubMed] [Google Scholar]
  • 18.Juhasz P, Costello CE. Matrix-assisted laser desorption ionization time-of-flight mass spectrometry of underivatized and permethylated gangliosides. J Am Soc Mass Spectrom. 1992;3:785–796. doi: 10.1016/1044-0305(92)80001-2. [DOI] [PubMed] [Google Scholar]
  • 19.Caprioli RM, Farmer TB, Gile J. Molecular imaging of biological samples: localization of peptides and proteins using MALDI-TOF MS. Anal Chem. 1997;69:4751–4760. doi: 10.1021/ac970888i. [DOI] [PubMed] [Google Scholar]
  • 20.Rubakhin SS, Li L, Moroz TP, Sweedler JV. Characterization of the aplysia californica cerebral ganglion F cluster. J Neurophysiol. 1999;81:1251–1260. doi: 10.1152/jn.1999.81.3.1251. [DOI] [PubMed] [Google Scholar]
  • 21.Jackson SN, Wang H-YJ, Ugarov M, Egan T, Schultz JA, Woods AS. Direct tissue analysis of phospholipids in rat brain using MALDI-TOFMS and MALDI-ion mobility-TOFMS. J Am Soc Mass Spectrom. 2005;16:133–138. doi: 10.1016/j.jasms.2004.10.002. [DOI] [PubMed] [Google Scholar]
  • 22.Jackson SN, Wang H-YJ, Woods AS. Direct profiling of lipid distribution in brain tissue using MALDI-TOF MS. Anal Chem. 2005;77:4523–4527. doi: 10.1021/ac050276v. [DOI] [PubMed] [Google Scholar]
  • 23.Jackson SN, Yang H-YJ, Woods AS. In situ structural characterization of phosphatidylcholines in brain tissue using MALDI/TOF-TOF. J Am Soc Mass Spectrom. 2005;16:2052–2056. doi: 10.1016/j.jasms.2005.08.014. [DOI] [PubMed] [Google Scholar]
  • 24.Rujoi M, Estrada R, Yappert MC. In situ MALDI-TOF MS regional analysis of neutral phospholipids in lens tissue. Anal Chem. 2004;76:1657–1663. doi: 10.1021/ac0349680. [DOI] [PubMed] [Google Scholar]
  • 25.Touboul D, Piednoel H, Voisin V, et al. Changes of phospholipid composition within the dystrophic muscle by matrix-assisted laser desorption/ionization mass spectrometry and mass spectrometry imaging. Eur J Mass Spectrom (Chichester, Eng) 2004;10:657–664. doi: 10.1255/ejms.671. [DOI] [PubMed] [Google Scholar]
  • 26.Schwartz SA, Reyzer ML, Caprioli RM. Direct tissue analysis using matrix-assisted laser desorption/ionization mass spectrometry: practical aspects of sample preparation. J Mass Spectrom. 2003;38:699–708. doi: 10.1002/jms.505. [DOI] [PubMed] [Google Scholar]
  • 27.Agranoff BW, Benjamins JA, Hajra AK, et al. Lipids. In: Siegel GJ, et al., editors. Basic Neurochemistry: Molecular, Cellular, and Medical Aspects. 6th ed. Philadelphia, PA: Lippincott, Williams & Wilkins; 1999. pp. 47–67. [Google Scholar]
  • 28.Ma Y-C, Kim H-Y. Development of the on-line high-performance liquid chromatography/thermospray mass spectrometry method for the analysis of phospholipid molecular species in rat brain. Anal Biochem. 1995;226:293–301. doi: 10.1006/abio.1995.1228. [DOI] [PubMed] [Google Scholar]
  • 29.Sonnino S, Chigorno V. Ganglioside molecular species containing C18-and C20-sphingosine in mammalian nervous tissues and neuronal cell cultures. Biochim Biophys Acta. 2000;1469:63–77. doi: 10.1016/s0005-2736(00)00210-8. [DOI] [PubMed] [Google Scholar]
  • 30.Schwarz A, Futerman AH. The localization of gangliosides in neurons of the central nervous system: the use of anti-ganglioside antibodies. Biochim Biophys Acta. 1996;1286:247–267. doi: 10.1016/s0304-4157(96)00011-1. [DOI] [PubMed] [Google Scholar]
  • 31.Heffer-Lauc M, Lauc G, Nimrichter L, Fromholt SE, Schnaar RL. Membrane redistribution of gangliosides and glycosylphosphatidylinositol-anchored proteins in brain tissue sections under conditions of lipid raft isolation. Biochim Biophys Acta. 2005;1686:200–208. doi: 10.1016/j.bbalip.2004.10.002. [DOI] [PubMed] [Google Scholar]
  • 32.Molander M, Berthold C-H, Persson H, Fredman P. Immunostaining of ganglioside GD1b, GD3 and GM1 in rat cerebellum: cellular layer and cell type specific associations. J Neurosci Res. 2000;60:531–542. doi: 10.1002/(SICI)1097-4547(20000515)60:4<531::AID-JNR12>3.0.CO;2-6. [DOI] [PubMed] [Google Scholar]
  • 33.Spengler B, Hubert M. Scanning microprobe matrix-assisted laser desorption ionization (SMALDI) mass spectrometry: instrumentation for sub-micrometer resolved LDI and MALDI surface analysis. J Am Soc Mass Spectrom. 2002;13:735–748. doi: 10.1016/S1044-0305(02)00376-8. [DOI] [PubMed] [Google Scholar]

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