Microscopic imaging mass spectrometry assisted by on‐tissue chemical derivatization for visualizing multiple amino acids in human colon cancer xenografts

Toue, Sakino; Sugiura, Yuki; Kubo, Akiko; Ohmura, Mitsuyo; Karakawa, Sachise; Mizukoshi, Toshimi; Yoneda, Junya; Miyano, Hiroshi; Noguchi, Yasushi; Kobayashi, Tsuyoshi; Kabe, Yoshio; Suematsu, Makoto

doi:10.1002/pmic.201300041

Cited by 66 publications

(70 citation statements)

References 27 publications

(60 reference statements)

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“…The reduced nitrogen associated with these amino acids can be used for additional de novo synthesis of amino acids (Bewley et al, 2013). Because of their low ionization efficiency and amphiprotic nature, amino acids are difficult to analyze by MALDI-MSI (Toue et al, 2014). Despite this known difficulty, three amino acids were reliably detected in the MSI experiments, these being Lys, Arg, and Pro ( Fig.…”

Section: Heterogeneous Distribution Of the Mobilization Of Seed Storamentioning

confidence: 99%

Spatial Mapping and Profiling of Metabolite Distributions during Germination

et al. 2017

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Germination is a highly complex process by which seeds begin to develop and establish themselves as viable organisms. In this study, we utilize a combination of gas chromatography-mass spectrometry, liquid chromatography-fluorescence, and mass spectrometry imaging approaches to profile and visualize the metabolic distributions of germinating seeds from two different inbreds of maize (Zea mays) seeds, B73 and Mo17. Gas chromatography and liquid chromatography analyses demonstrate that the two inbreds are highly differentiated in their metabolite profiles throughout the course of germination, especially with regard to amino acids, sugar alcohols, and small organic acids. Crude dissection of the seed followed by gas chromatography-mass spectrometry analysis of polar metabolites also revealed that many compounds were highly sequestered among the various seed tissue types. To further localize compounds, matrix-assisted laser desorption/ionization mass spectrometry imaging was utilized to visualize compounds in fine detail in their native environments over the course of germination. Most notably, the fatty acyl chain-dependent differential localization of phospholipids and triacylglycerols was observed within the embryo and radicle, showing correlation with the heterogeneous distribution of fatty acids. Other interesting observations include unusual localization of ceramides on the endosperm/scutellum boundary and subcellular localization of ferulate in the aleurone.Plants use seeds as the propagule to ensure reproduction to the next generation, and over the past 10,000 years, human civilizations have established agricultural practices to ensure a seed-based food supply (Larson et al., 2014). Therefore, deciphering the processes that enable seeds to perform their biological functions is of importance in understanding how plants are propagated and also is of practical importance to improve agriculture. Seeds are designed to survive long periods of dormancy in a relatively dry state, and the process of germination is initiated by the imbibition of water. During this germination process, many metabolic changes occur, most of which are associated with the catabolism of seed storage products (proteins, polysaccharides, and lipids) into metabolically usable, simpler chemical forms that are either used as precursors to assemble the growing seedling or are oxidized via energy-producing biochemical pathways to thermodynamically support growth (Bewley, 1997(Bewley, , 2001.The specific metabolic processes that support seed germination are somewhat dependent on the taxonomic clade of the plant, which determines seed tissue/ organ organization and the nature of the seed storage compounds. Specifically, the seeds of the Poaceae family of monocots are characterized by a starch-and protein-filled endosperm, and their catabolism by digestive enzymes produced in the outermost layer of the endosperm (i.e. the aleurone) provides the carbonbased and nitrogenous precursors for the growth of the embryo, which is composed of the embryonic ax...

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Section: Heterogeneous Distribution Of the Mobilization Of Seed Storamentioning

confidence: 99%

Spatial Mapping and Profiling of Metabolite Distributions during Germination

et al. 2017

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“…The overall sensitivity of MALDI-MSI can be enhanced to some extent by optimizing the type of matrix used, the matrix solvent composition [20], the method of matrix application [21], and the tissue clean up protocol [22], or by chemical derivatization [23][24][25][26][27].…”

Section: Introductionmentioning

confidence: 99%

Pyrylium Salts as Reactive Matrices for MALDI-MS Imaging of Biologically Active Primary Amines

Shariatgorji

Nilsson

Källback

et al. 2015

J. Am. Soc. Mass Spectrom.

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Abstract. Many neuroactive substances, including endogenous biomolecules, environmental compounds, and pharmaceuticals possess primary amine functional groups. Among these are catecholamine neurotransmitters (e.g., dopamine), many substituted phenethylamines (e.g., amphetamine), as well as amino acids and neuropeptides. In most cases, mass spectrometric (ESI and MALDI) analyses of trace amounts of such compounds are challenging because of their poor ionization properties. We present a method for chemical derivatization of primary amines by reaction with pyrylium salts that facilitates their detection by MALDI-MS and enables the imaging of primary amines in brain tissue sections. A screen of pyrylium salts revealed that the 2,4-diphenyl-pyranylium ion efficiently derivatizes primary amines and can be used as a reactive MALDI-MS matrix that induces both derivatization and desorption. MALDI-MS imaging with such matrix was used to map the localization of dopamine and amphetamine in brain tissue sections and to quantitatively map the distribution of the neurotoxin β-N-methylamino-L-alanine.

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“…By expanding this concept, not only the exogenous drug but also the endogenous metabolites, including steroid hormones 54) (Fig. 4B), minor amino acids, 27) and monoamine neurotransmitters along with their precursor/decomposed metabolites 55,56) (Fig. 4C), were successfully visualized.…”

Section: On-tissue Derivatization Of Target Metabolites Enhances mentioning

confidence: 99%

“…In particular, we have developed several key techniques, including (i) a sample preparation procedure that eliminates the common e ect of postmortem (PM) degradation of labile metabolites, 26) and (ii) on-tissue derivatization of metabolites that could enhance the analyte ionization e ciency. 27) ese techniques have enabled visualization of diverse metabolite species, including not only abundant phospholipids [28][29][30] but also metabolites present in trace amounts such as minor amino acids, 31) nucleotides, 32,33) neurotransmitters, [34][35][36] and bioactive lipids, 37) in various tissues of diseased model animals (as summarized in Fig. 1).…”

Section: Introductionmentioning

confidence: 99%

Development of an Imaging Mass Spectrometry Technique for Visualizing Localized Cellular Signaling Mediators in Tissues

Honda

Suematsu

2015

Mass Spectrometry

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In vivo concentrations of cellular signaling mediators such as in ammatory mediators are normally maintained at very low levels due to their strong ability to induce a biological response. e production, di usion, and decomposition of such mediators are spatio-temporally regulated. erefore, in order to understand biochemical basis of disease progression and develop new therapeutic strategies, it is important to understand the spatiotemporal dynamics of the signaling mediators in vivo, during the progression of disorders, e.g., chronic in ammatory diseases; however, the lack of e ective imaging technology has made it di cult to determine their localizations in vivo. Such characterization requires technical breakthroughs, including molecular imaging methods that are sensitive enough to detect low levels of metabolites in the heterogeneous tissue regions in diseased organs. We and other groups have attempted to ll this technical gap by developing highly sensitive imaging mass spectrometry (IMS) technologies. To date, we have established two key techniques toward this goal, including (i) a sample preparation procedure that has eliminated the problem of the postmortem degradation of labile metabolites, and (ii) on-tissue derivatization of metabolites, which can enhance analyte ionization e ciency. Here, we review recent progress in the development of these technologies as well as how the highly sensitive IMS technique has contributed to increasing understanding of the biochemical basis of disease mechanisms, discovery of new diagnostic markers, and development of new therapies.Please cite this article as: Mass Spectrom (Tokyo) 2015; 4(1): A0040

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Microscopic imaging mass spectrometry assisted by on‐tissue chemical derivatization for visualizing multiple amino acids in human colon cancer xenografts

Cited by 66 publications

References 27 publications

Spatial Mapping and Profiling of Metabolite Distributions during Germination

Spatial Mapping and Profiling of Metabolite Distributions during Germination

Pyrylium Salts as Reactive Matrices for MALDI-MS Imaging of Biologically Active Primary Amines

Development of an Imaging Mass Spectrometry Technique for Visualizing Localized Cellular Signaling Mediators in Tissues

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