Abstract
Metals and other trace elements play an important role in many physiological processes in all biological systems. Characterization of precise metal concentrations, their spatial distribution, and chemical speciation in individual cells and cell compartments will provide much needed information to explore the metallome in health and disease. Synchrotron-based X-ray fluorescent microscopy (SXRF) is the ideal tool to quantitatively measure trace elements with high sensitivity at high resolution. SXRF is based on the intrinsic fluorescent properties of each element and is therefore element specific. Recent advances in synchrotron technology and optimization of sample preparation have made it possible to image metals in mammalian tissue with submicron resolution. In combination with correlative methods, SXRF can now, for example, determine the amount and oxidation state of trace elements in intra-cellular compartments and identify cell-specific changes in the metal ion content during development or disease progression.
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Ala A, Walker AP, Ashkan K, Dooley JS, Schilsky ML (2007) Wilson’s disease. Lancet 369:397–408. doi:10.1016/S0140-6736(07)60196-2
Becker JS, Mounicou S, Zoriy MV, Becker JS, Lobinski R (2008) Analysis of metal-binding proteins separated by non-denaturating gel electrophoresis using matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) and laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS). Talanta 76:1183–1188. doi:10.1016/j.talanta.2008.05.023
Becker JS, Zoriy M, Becker JS, Pickhardt C, Damoc E, Juhacz G, Palkovits M, Przybylski M (2005) Determination of phosphorus-, copper-, and zinc-containing human brain proteins by LA-ICPMS and MALDI-FTICR-MS. Anal Chem 77:5851–5860. doi:10.1021/ac0506579
Buiakova OI, Xu J, Lutsenko S, Zeitlin S, Das K, Das S, Ross BM, Mekios C, Scheinberg IH, Gilliam TC (1999) Null mutation of the murine ATP7B (Wilson disease) gene results in intracellular copper accumulation and late-onset hepatic nodular transformation. Hum Mol Genet 8:1665–1671. doi:10.1093/hmg/8.9.1665
Choi DW, Koh JY (1998) Zinc and brain injury. Annu Rev Neurosci 21:347–375. doi:10.1146/annurev.neuro.21.1.347
Danks DM, Campbell PE, Stevens BJ, Mayne V, Cartwright E (1972) Menkes’s kinky hair syndrome. An inherited defect in copper absorption with widespread effects. Pediatrics 50:188–201
Dillon CT, Lay PA, Kennedy BJ, Stampfl AP, Cai Z, Ilinski P, Rodrigues W, Legnini DG, Lai B, Maser J (2002) Hard X-ray microprobe studies of chromium(VI)-treated V79 Chinese hamster lung cells: intracellular mapping of the biotransformation products of a chromium carcinogen. J Biol Inorg Chem 7:640–645. doi:10.1007/s00775-002-0343-5
Finney L, Mandava S, Ursos L, Zhang W, Rodi D, Vogt S, Legnini D, Maser J, Ikpatt F, Olopade OI, Glesne D (2007) X-ray fluorescence microscopy reveals large-scale relocalization and extracellular translocation of cellular copper during angiogenesis. Proc Natl Acad Sci USA 104:2247–2252. doi:10.1073/pnas.0607238104
Hall MD, Dillon CT, Zhang M, Beale P, Cai Z, Lai B, Stampfl AP, Hambley TW (2003) The cellular distribution and oxidation state of platinum(II) and platinum(IV) antitumour complexes in cancer cells. J Biol Inorg Chem 8:726–732. doi:10.1007/s00775-003-0471-6
Hanaichi T, Kidokoro R, Hayashi H, Sakamoto N (1984) Electron probe X-ray analysis on human hepatocellular lysosomes with copper deposits: copper binding to a thiol-protein in lysosomes. Lab Invest 51:592–597
Harris HH, Levina A, Dillon CT, Mulyani I, Lai B, Cai Z, Lay PA (2005) Time-dependent uptake, distribution and biotransformation of chromium(VI) in individual and bulk human lung cells: application of synchrotron radiation techniques. J Biol Inorg Chem 10:105–118. doi:10.1007/s00775-004-0617-1
Huster D, Finegold MJ, Morgan CT, Burkhead JL, Nixon R, Vanderwerf SM, Gilliam CT, Lutsenko S (2006) Consequences of copper accumulation in the livers of the atp7b−/− (Wilson disease gene) knockout mice. Am J Pathol 168:423–434. doi:10.2353/ajpath.2006.050312
Kemner KM, Kelly SD, Lai B, Maser J, O’Loughlin EJ, Sholto-Douglas D, Cai Z, Schneegurt MA, Kulpa CF Jr, Nealson KH (2004) Elemental and redox analysis of single bacterial cells by X-ray microbeam analysis. Science 306:686–687. doi:10.1126/science.1103524
Kirz J, Sayre D, Dilger J (1978) Short Wavelength Microscopy. NY Academy of Science, New York
Koh JY, Suh SW, Gwag BJ, He YY, Hsu CY, Choi DW (1996) The role of zinc in selective neuronal death after transient global cerebral ischemia. Science 272:1013–1016. doi:10.1126/science.272.5264.1013
Lahner B, Gong J, Mahmoudian M, Smith EL, Abid KB, Rogers EE, Guerinot ML, Harper JF, Ward JM, McIntyre L, Schroeder JI, Salt DE (2003) Genomic scale profiling of nutrient and trace elements in Arabidopsis thaliana. Nat Biotechnol 21:1215–1221. doi:10.1038/nbt865
Loudianos G, Gitlin JD (2000) Wilson’s disease. Semin Liver Dis 20:353–364. doi:10.1055/s-2000-9389
McCrea RP, Harder SL, Martin M, Buist R, Nichol H (2008) A comparison of rapid-scanning X-ray fluorescence mapping and magnetic resonance imaging to localize brain iron distribution. Eur J Radiol 68:109–113
McRae R, Lai B, Vogt S, Fahrni CJ (2006) Correlative microXRF and optical immunofluorescence microscopy of adherent cells labeled with ultrasmall gold particles. J Struct Biol 155:22–29. doi:10.1016/j.jsb.2005.09.013
Miller LM, Wang Q, Telivala TP, Smith RJ, Lanzirotti A, Miklossy J (2006) Synchrotron-based infrared and X-ray imaging shows focalized accumulation of Cu and Zn co-localized with beta-amyloid deposits in Alzheimer’s disease. J Struct Biol 155:30–37
Nakazato K, Nagamine T, Suzuki K, Kusakabe T, Moon HD, Oikawa M, Sakai T, Arakawa K (2008) Subcellular changes of essential metal shown by in-air micro-PIXE in oral cadmium-exposed mice. Biometals 21:83–91. doi:10.1007/s10534-007-9095-6
Paunesku T, Rajh T, Wiederrecht G, Maser J, Vogt S, Stojicevic N, Protic M, Lai B, Oryhon J, Thurnauer M, Woloschak G (2003) Biology of TiO2-oligonucleotide nanocomposites. Nat Mater 2:343–346. doi:10.1038/nmat875
Pickering IJ, Gumaelius L, Harris HH, Prince RC, Hirsch G, Banks JA, Salt DE, George GN (2006) Localizing the biochemical transformations of arsenate in a hyperaccumulating fern. Environ Sci Technol 40:5010–5014. doi:10.1021/es052559a
Pickering IJ, Prince RC, Salt DE, George GN (2000) Quantitative, chemically specific imaging of selenium transformation in plants. Proc Natl Acad Sci USA 97:10717–10722. doi:10.1073/pnas.200244597
Roomans GM (1988) Introduction to X-ray microanalysis in biology. J Electron Microsc Tech 9:3–17. doi:10.1002/jemt.1060090103
Roomans GM, Von Euler A (1996) X-ray microanalysis in cell biology and cell pathology. Cell Biol Int 20:103–109. doi:10.1006/cbir.1996.0014
Sham TK, Kim PSG, Ngo H, Chakrabarti S, Adams PC (2005) X-ray Microspectroscopy of Hemochromatosis Liver and Diabetic Mice Kidney Tissues: Preliminary Observations. Phys Scr T 115:1047–1049. doi:10.1238/Physica.Topical.115a01047
Sparks CJ (1980) Synchrotron Radiation Research. Plenum Press, New York
Szokefalvi-Nagy Z (1994) Applications of PIXE in the life sciences. Biol Trace Elem Res 43–45:73–78. doi:10.1007/BF02917301
Twining BS, Baines SB, Fisher NS, Maser J, Vogt S, Jacobsen C, Tovar-Sanchez A, Sanudo-Wilhelmy SA (2003) Quantifying trace elements in individual aquatic protist cells with a synchrotron X-ray fluorescence microprobe. Anal Chem 75:3806–3816. doi:10.1021/ac034227z
Van Espen P (2002) Spectrum Evaluation Handbook of X-ray Spectrometry. Marcel Dekker, New York
Vogt S (2003) Maps: A set of software tools for analysis and visualization of 3D X-ray fluorescent datasets. J Phys IV 104:635–638. doi:10.1051/jp4:20030160
Waern JB, Harris HH, Lai B, Cai Z, Harding MM, Dillon CT (2005) Intracellular mapping of the distribution of metals derived from the antitumor metallocenes. J Biol Inorg Chem 10:443–452. doi:10.1007/s00775-005-0649-1
Waggoner DJ, Bartnikas TB, Gitlin JD (1999) The role of copper in neurodegenerative disease. Neurobiol Dis 6:221–230. doi:10.1006/nbdi.1999.0250
Yang L, McRae R, Henary MM, Patel R, Lai B, Vogt S, Fahrni CJ (2005) Imaging of the intracellular topography of copper with a fluorescent sensor and by synchrotron X-ray fluorescence microscopy. Proc Natl Acad Sci USA 102:11179–11184. doi:10.1073/pnas.0406547102
Yun W, Lai B, Cai Z, Maser J, Legnini D, Gluskin E, Chen Z, Krasnoperova A, Valdimirsky Y, Cerrina F, Di Fabrizio E, Gentili M (1999) Nanometer Focusing of Hard X-Rays by Phase Zone Plates. Rev Sci Instrum 70:2238–2241. doi:10.1063/1.1149744
Zierold K (2000) Heavy metal cytotoxicity studied by electron probe X-ray microanalysis of cultured rat hepatocytes. Toxicol In Vitro 14:557–563. doi:10.1016/S0887-2333(00)00049-7
Acknowledgments
The authors would like to gratefully acknowledge the use of the facilities at the Advanced Photon Source. This work was supported by a National Institutes of Health Grant GM067166 to SL, the use of the Advanced Photon Source was supported by the U.S. Department of Energy, Office of Science Contract DE-AC-02-06CH11357
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Ralle, M., Lutsenko, S. Quantitative imaging of metals in tissues. Biometals 22, 197–205 (2009). https://doi.org/10.1007/s10534-008-9200-5
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DOI: https://doi.org/10.1007/s10534-008-9200-5