In Situ Primary Metabolites Localization on a Rat Brain Section by Chemical Mass Spectrometry Imaging

Benabdellah, Farida; Touboul, David; Brunelle, Alain; Laprévôte, Olivier

doi:10.1021/ac9005364

Cited by 95 publications

(80 citation statements)

References 16 publications

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“…As shown in Figure 7, MALDI-MS analysis in the negative ion mode using 9-AA as the matrix yielded clear AMP, ADP, and ATP signals on the brain tissue, consistent with previous studies (4,7,30). Moreover, signals for NADH and cADPR were detected for the first time.…”

Section: Imaging Mssupporting

confidence: 89%

Paradoxical ATP Elevation in Ischemic Penumbra Revealed by Quantitative Imaging Mass Spectrometry

Hattori

Kajimura

Hishiki

et al. 2010

Antioxidants & Redox Signaling

102

133

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Local responses of energy metabolism during brain ischemia are too heterogeneous to decipher redox distribution between anoxic core and adjacent salvageable regions such as penumbra. Imaging mass spectrometry combined by capillary electrophoresis=mass spectrometry providing quantitative metabolomics revealed spatiotemporal changes in adenylates and NADH in a mouse middle-cerebral artery occlusion model. Unlike the core where ATP decreased, the penumbra displayed paradoxical elevation of ATP despite the constrained blood supply. It is noteworthy that the NADH elevation in the ischemic region is clearly demarcated by the ATPdepleting core. Results suggest that metabolism in ischemic penumbra does not respond passively to compromised circulation, but actively compensates energy charges. Antioxid. Redox Signal. 13, 1157-1167. Quantitative Imaging Mass Spectrometry as a Novel Tactics to Decipher Metabolic Dynamics of Brain IschemiaT o develop neuroprotective therapies for cerebrovascular diseases, it is necessary to characterize spatiotemporal changes in energy metabolism occurring at two functionally defined areas of ischemic brain: one is the ischemic core, which is unsalvageable, and another is its adjacent zone termed penumbra, which is salvageable by interventions. Such characterization requires technical breakthrough including simultaneous identification of multiple compounds comprising energy metabolic systems and quantitative analytical methods sensitive enough to detect low levels of metabolites in the heterogeneous regions of ischemic brain. To achieve these requirements, we combined two types of mass spectrometry (MS): matrix-assisted laser desorption ionization (MALDI)=MS and capillary electrophoresis=electrospray ionization (CE=ESI)=MS. Unlike conventional spectroscopic techniques with which chemical profiles are obtained from one selected volume at a time, MALDI=MS has strengths in visualizing multiple metabolites in discrete areas with a single laser ablation (10, 26, 32). However, it still requires further efforts to be supported for quantification. By contrast, CE=ESI=MS excels in quantification of metabolites (15,22,23) because ESI is efficient in transferring molecules from liquid phase to gas phase. Comparison of transcriptional expression profiles with CE=ESI= MS-based metabolomics previously led us to hypothesize the existence of novel metabolic pathways (33) and their regulatory mechanisms (15,22,23). However, it removes spatial distribution of molecules due to tissue homogenization to extract metabolites.Using imaging MS (IMS) combined with CE=ESI=MS, we herein constructed maps of adenine nucleotides whereby abundance of these metabolites was assigned in absolute terms, that is, mmol=g tissue. Such assignment of contents made it possible to directly compare patterns of biochemical derangements in and around the ischemic core at different time points during infarction. Our results suggest that, unlike the core, the penumbra displays paradoxical elevation of ATP despite the constrained b...

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Section: Imaging Mssupporting

confidence: 89%

Paradoxical ATP Elevation in Ischemic Penumbra Revealed by Quantitative Imaging Mass Spectrometry

Hattori

Kajimura

Hishiki

et al. 2010

Antioxidants & Redox Signaling

102

133

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“…Sections were attached onto indium-tin oxide (ITO)-coated glass slides (Bruker Daltonics, Billerica, MA, USA) with electrically conducting double-adhesive tape (Shimadzu Corporation, Kyoto, Japan). Prepared tissues were coated with 9-aminoacridine as the matrix (10 mg/ml dissolved in 80% ethanol) (Benabdellah et al, 2009) by manually spraying with an artistic brush (Procon Boy FWA Platinum, Mr. Hobby, Tokyo, Japan). The matrix was simultaneously applied to multiple tissue sections in order to maintain consistent analyte extraction and co-crystallization conditions (Setou, 2010;Sugiura et al, 2009).…”

Section: Maldi-imsmentioning

confidence: 99%

Rewiring of embryonic glucose metabolism via suppression of PFK-1 and aldolase during mouse chorioallantoic branching

Miyazawa¹,

Yamaguchi²,

Honda³

et al. 2017

Journal of Cell Science

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Adapting the energy metabolism state to changing bioenergetic demands is essential for mammalian development accompanying massive cell proliferation and cell differentiation. However, it remains unclear how developing embryos meet the changing bioenergetic demands during the chorioallantoic branching (CB) stage, when the maternal-fetal exchange of gases and nutrients is promoted. In this study, using metabolome analysis with mass-labeled glucose, we found that developing embryos redirected glucose carbon flow into the pentose phosphate pathway via suppression of the key glycolytic enzymes PFK-1 and aldolase during CB. Concomitantly, embryos exhibited an increase in lactate pool size and in the fractional contribution of glycolysis to lactate biosynthesis. Imaging mass spectrometry visualized lactate-rich tissues, such as the dorsal or posterior neural tube, somites and head mesenchyme. Furthermore, we found that the heterochronic gene Lin28a could act as a regulator of the metabolic changes observed during CB. Perturbation of glucose metabolism rewiring by suppressing Lin28a downregulation resulted in perinatal lethality. Thus, our work demonstrates that developing embryos rewire glucose metabolism following CB for normal development.

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“…MALDI-MS, a widely used MS technology for analyses of protein and nucleotide polymers, possesses the potential for rapid analysis of sulfatides and has showed success in directly imaging and detecting sulfatide species from biological tissue samples (28)(29)(30)(31)(32). Quantitation of sulfatide species has previously been demonstrated by MALDI-MS after converting sulfatides to their lyso forms by saponifi cation and sample purifi cation using a C18 column or C18 tips ( 22,23 ).…”

Section: Preparation Of Lipid Extractsmentioning

confidence: 99%

Selective desorption/ionization of sulfatides by MALDI-MS facilitated using 9-aminoacridine as matrix

Cheng

Sun

Yang

et al. 2010

Journal of Lipid Research

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In Situ Primary Metabolites Localization on a Rat Brain Section by Chemical Mass Spectrometry Imaging

Cited by 95 publications

References 16 publications

Paradoxical ATP Elevation in Ischemic Penumbra Revealed by Quantitative Imaging Mass Spectrometry

Paradoxical ATP Elevation in Ischemic Penumbra Revealed by Quantitative Imaging Mass Spectrometry

Rewiring of embryonic glucose metabolism via suppression of PFK-1 and aldolase during mouse chorioallantoic branching

Selective desorption/ionization of sulfatides by MALDI-MS facilitated using 9-aminoacridine as matrix

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