Imaging of peptides in the rat brain using MALDI-FTICR mass spectrometry

Analytical methods are pursued to measure the identity and location of biomolecules down to the subcellular (µm) level. Available mass spectrometric imaging methods either compromise localization accuracy or identification accuracy in their analysis of surface biomolecules. In this study, imaging FTICR-MS is applied for the spatially resolved mass analysis of rat brain tissue with the aim to optimize protein identification by the high mass accuracy and online MS/MS capabilities of the technique. Mass accuracies up to 6 ppm were obtained in the direct MALDI-analysis of the tissue together with a spatial resolution of 200 µm. The spatial distributions of biomolecules differing in mass by less than 0.1 Da could be resolved, and are shown to differ significantly. Online MS/MS analysis of selected ions was demonstrated. A comparison of the FTICR-MS imaging results with stigmatic TOF imaging on the same sample is presented. To reduce the extended measuring times involved, it is recommended to restrict the FTICR-MS analyses to areas of interest as can be preselected by other, faster imaging methods.

[1]  B. Cargile,et al.  Synthesis/degradation ratio mass spectrometry for measuring relative dynamic protein turnover. , 2004, Analytical chemistry.

[2]  F. Baas,et al.  The unfolded protein response affects neuronal cell cycle protein expression: Implications for Alzheimer's disease pathogenesis , 2006, Experimental Gerontology.

[3]  T. Dierks,et al.  Multiple Sulfatase Deficiency Is Caused by Mutations in the Gene Encoding the Human Cα-Formylglycine Generating Enzyme , 2003, Cell.

[4]  Per Malmberg,et al.  Bioimaging TOF‐SIMS: localization of cholesterol in rat kidney sections , 2004, FEBS letters.

[5]  C. Burd,et al.  Dual prenylation is required for Rab protein localization and function. , 2003, Molecular biology of the cell.

[6]  J. Lausmaa,et al.  Mass spectrometric imaging of lipids in brain tissue. , 2004, Analytical chemistry.

[7]  Richard M Caprioli,et al.  Increased levels of ubiquitin in the 6-OHDA-lesioned striatum of rats. , 2005, Journal of proteome research.

[8]  Lingjun Li,et al.  In situ tissue analysis of neuropeptides by MALDI FTMS in-cell accumulation. , 2004, Analytical chemistry.

[9]  H. Lipshitz,et al.  Role of Adducin-like (hu-li tai shao) mRNA and protein localization in regulating cytoskeletal structure and function during Drosophila Oogenesis and early embryogenesis. , 1996, Developmental Genetics.

[10]  Gert B. Eijkel,et al.  Using matrix peaks to map topography: increased mass resolution and enhanced sensitivity in chemical imaging. , 2003, Analytical chemistry.

[11]  D. A. Reed,et al.  A time-of-flight secondary ion microscope , 1990 .

[12]  H. Münzberg,et al.  N-acetylation of hypothalamic α-melanocyte-stimulating hormone and regulation by leptin , 2004 .

[13]  L. McDonnell,et al.  High-spatial resolution mass spectrometric imaging of peptide and protein distributions on a surface. , 2004, Analytical chemistry.

[14]  P. Svenningsson,et al.  Decreased striatal levels of PEP-19 following MPTP lesion in the mouse. , 2006, Journal of proteome research.

[15]  S. Hanash.  Disease proteomics : Proteomics , 2003 .

[16]  Richard D. Smith.  Evolution of esi–mass spectrometry and fourier transform ion cyclotron resonance for proteomics and other biological applications , 2000 .

[17]  I. Grundke‐Iqbal,et al.  Glycosylation of microtubule–associated protein tau: An abnormal posttranslational modification in Alzheimer's disease , 1996, Nature Medicine.

[18]  John C. Vickerman,et al.  ToF-SIMS : surface analysis by mass spectrometry , 2001 .

[19]  R. Gijbels,et al.  Metal-assisted secondary ion mass spectrometry: influence of Ag and Au deposition on molecular ion yields. , 2004, Analytical chemistry.

[20]  B. Schueler.  Microscope imaging by time-of-flight secondary ion mass spectrometry , 1992 .

[21]  R. Aebersold,et al.  Mass spectrometry-based proteomics , 2003, Nature.

[22]  Jonathan V Sweedler,et al.  Spatial profiling invertebrate ganglia using MALDI MS , 2003, Journal of the American Society for Mass Spectrometry.

[23]  Bernhard Spengler,et al.  Scanning microprobe matrix-assisted laser desorption ionization (SMALDI) mass spectrometry: Instrumentation for sub-micrometer resolved LDI and MALDI surface analysis , 2002, Journal of the American Society for Mass Spectrometry.

[24]  Michelle L. Reyzer,et al.  Direct tissue analysis using matrix-assisted laser desorption/ionization mass spectrometry: practical aspects of sample preparation. , 2003, Journal of mass spectrometry : JMS.

[25]  F W McLafferty,et al.  Two-dimensional mass spectrometry of biomolecules at the subfemtomole level. , 1998, Current opinion in chemical biology.

[26]  R. Gijbels,et al.  Organic SIMS: the influence of time on the ion yield enhancement by silver and gold deposition , 2004 .

[27]  R. Heeren,et al.  Effect of local matrix crystal variations in matrix-assisted ionization techniques for mass spectrometry. , 2003, Analytical chemistry.

[28]  Richard M Caprioli,et al.  Molecular profiling of experimental Parkinson's disease: direct analysis of peptides and proteins on brain tissue sections by MALDI mass spectrometry. , 2004, Journal of proteome research.

[29]  A. Marshall,et al.  Fourier transform ion cyclotron resonance mass spectrometry: a primer. , 1998, Mass spectrometry reviews.

[30]  Koichi Tanaka,et al.  Protein and polymer analyses up to m/z 100 000 by laser ionization time-of-flight mass spectrometry , 1988 .

[31]  F. Holsboer,et al.  Release of Vasopressin within the Rat Paraventricular Nucleus in Response to Emotional Stress: A Novel Mechanism of Regulating Adrenocorticotropic Hormone Secretion? , 1996, The Journal of Neuroscience.

[32]  S. Fields,et al.  Protein analysis on a proteomic scale , 2003, Nature.

[33]  R. L. Hunter,et al.  High-accuracy molecular mass determination for peptides and proteins by Fourier transform mass spectrometry. , 1994, Analytical chemistry.

[34]  P. Bertrand,et al.  Sample metallization for performance improvement in desorption/ionization of kilodalton molecules: quantitative evaluation, imaging secondary ion MS, and laser ablation. , 2003, Analytical chemistry.

[35]  L. Vaeck,et al.  Static secondary ion mass spectrometry (S-SIMS) Part 1: methodology and structural interpretation , 1999 .

[36]  M. Karas,et al.  Matrix-assisted ultraviolet laser desorption of non-volatile compounds , 1987 .

[37]  Kees Jalink,et al.  Gold-enhanced biomolecular surface imaging of cells and tissue by SIMS and MALDI mass spectrometry. , 2006, Analytical chemistry.

[38]  R. Hensel,et al.  Electrospray sample preparation for improved quantitation in matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. , 1997, Rapid communications in mass spectrometry : RCM.

[39]  S. Hanash,et al.  Disease proteomics , 2003, Nature.

[40]  J. Burbach,et al.  Immunohistochemical localization of the vasopressin V1b receptor in the rat brain and pituitary gland: anatomical support for its involvement in the central effects of vasopressin. , 2001, Endocrinology.

[41]  C. Wilkins,et al.  High resolution laser desorption/ionization Fourier transform mass spectrometry , 1994 .

[42]  Sander R Piersma,et al.  Subcellular imaging mass spectrometry of brain tissue. , 2005, Journal of mass spectrometry : JMS.

[43]  R. Heeren,et al.  A modular data and control system to improve sensitivity, selectivity, speed of analysis, ease of use, and transient duration in an external source FTICR-MS , 2004 .

[44]  K. Owens,et al.  Investigations of matrix-assisted laser desorption/ionization sample preparation by time-of-flight secondary ion mass spectrometry , 1999 .

[45]  L. McDonnell,et al.  Higher sensitivity secondary ion mass spectrometry of biological molecules for high resolution, chemically specific imaging , 2006, Journal of the American Society for Mass Spectrometry.

[46]  Ludwig,et al.  Dendritic Release of Vasopressin and Oxytocin , 1998, Journal of neuroendocrinology.

[47]  M. Witt,et al.  Matrix-assisted laser desorption/ionization fourier transform ion cyclotron resonance mass spectrometry with pulsed in-source collision gas and in-source ion accumulation. , 2000, Rapid communications in mass spectrometry : RCM.

[48]  P. Chaurand,et al.  Profiling and imaging proteins in tissue sections by MS. , 2004, Analytical chemistry.

[49]  A. Altelaar,et al.  Direct molecular imaging of Lymnaea stagnalis nervous tissue at subcellular spatial resolution by mass spectrometry. , 2005, Analytical chemistry.

[50]  M. Stoeckli,et al.  Imaging mass spectrometry: A new technology for the analysis of protein expression in mammalian tissues , 2001, Nature Medicine.