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

Glycoconj J. 2021 Apr;38(2):167-175. doi: 10.1007/s10719-021-09984-w. Epub 2021 Mar 12.

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.

Keywords: Derivatization; MALDI-mass spectrometry imaging (MALDI-MSI); N-glycan; Non-alcoholic steatohepatitis (NASH).

MeSH terms

  • Animals
  • Fetuins / chemistry
  • Liver / chemistry*
  • Liver / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • N-Acetylneuraminic Acid / chemistry*
  • Non-alcoholic Fatty Liver Disease / pathology*
  • Paraffin Embedding
  • Polysaccharides / analysis*
  • Polysaccharides / chemistry
  • Spectrometry, Mass, Electrospray Ionization / methods
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / methods*
  • Tissue Fixation / methods

Substances

  • Fetuins
  • Polysaccharides
  • N-Acetylneuraminic Acid