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MALDI-TOF mass spectrometry imaging for N-glycans on FFPE tissue sections of mouse NASH liver through Sialic acid Benzylamidation

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Abstract

Glycans play an important physiological role and are drawing attention as biomarkers that capture pathophysiological changes. Glycans can be detected by mass spectrometry, but recently matrix-assisted laser desorption/ionization- mass spectrometry imaging (MALDI-MSI) has enabled the visualization of glycans distribution on tissues. In this study, focusing on sialylated glycan (sialoglycans), we investigated the amidation reaction used to visualize glycans distribution, and developed a method of sialic acid derivatization by benzylamidation which is more sensitive than conventional amidation. Furthermore, we adapted this method for visualizing glycans in formalin-fixed paraffin-embedded (FFPE) liver tissue from normal mice and non-alcoholic steatohepatitis (NASH) model mice using MALDI-MSI. As a result, an increase in the distribution of glycan N-Acetylneuraminic acid-(NeuAc) ions was observed in the NASH mouse liver, and the change in glycan structure in the NASH model was clarified.

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Data availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

Abbreviations

MALDI -MSI:

matrix-assisted laser desorption/ionization- mass spectrometry imaging

FFPE:

formalin-fixed paraffin-embedded

NASH:

non-alcoholic steatohepatitis

NeuAc:

N-Acetylneuraminic acid

NeuGc:

N-glycolylneuraminic acids

DHB:

dihydroxybenzoic acid

EDC:

1-ethyl-3-(3- (dimethylamino)propyl) carbodiimide

PyAOP:

(7-Azabenzotriazol-1-yloxy) tripyrrolidinophosphonium hexafluorophosphate

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Contributions

M.N. and K.M. conceived and designed the experiments; T.S. and A.W. performed the experiments; T.S., A.W., M.N., and K.M. analyzed the data; T.S., M.N., and K.M. wrote the paper.

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Correspondence to Kazuhiko Matsuo.

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Saito, T., Watanabe, A., Nakano, M. et al. MALDI-TOF mass spectrometry imaging for N-glycans on FFPE tissue sections of mouse NASH liver through Sialic acid Benzylamidation. Glycoconj J 38, 167–175 (2021). https://doi.org/10.1007/s10719-021-09984-w

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  • DOI: https://doi.org/10.1007/s10719-021-09984-w

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