Lipid Visualization Achieved Via Ultra-High-Resolution Imaging Mass Spectrometry

Key Points
・Ultra-high-resolution mass spectrometry used to visualize a sphingomyelin molecular species2 in mouse brain sections.・This study demonstrated the mechanism how the tissue distribution of sphingomyelin molecular species is regulated by particular synthase.

・These findings may lead to an understanding of the physiological functions of lipid molecules and the discovery of new diagnostic markers.
Overview
Recent studies have shown that lipids play an important role in various biological phenomena and the development of diseases. Visualizing the localization of lipid molecules is an effective method of studying their physiological functions, but it is difficult to visualize lipid molecules using conventional approaches. Therefore, we focused on sphingomyelin, an important lipid that comprises biomembranes, and used imaging mass spectroscopy3, a method of visualizing molecules using a mass spectrometer, to visualize sphingomyelin molecular species in tissue sections. In addition, by comparing the results obtained with the tissue distribution of the ceramide synthase4 family, we also revealed how localization of the sphingomyelin molecular species is regulated. These findings may lead to discoveries that reveal the physiological functions of lipid molecules including sphingomyelin, and the discovery of new diagnostic markers.This study was funded by a grant-in-aid from the Creation of Innovation Centers for Advanced Interdisciplinary Research Areas Program of the Ministry of Education, Culture, Sports, Science, and Technology.

 

1 – Mass spectrometry:Equipment for carrying out mass spectrometry. Mass spectrometry is a method in which a substance is dissociated into fine ion particles such as atoms and molecules by means of various ionization techniques. The mass-to-charge ratio is measured to separate and detect the substance.

2 – Sphingomyelin:A type of sphingolipid that has a polar group of phosphocholine, and has ceramide as a backbone. A large number of sphingomyelins exist within the cell membrane, and they are known as a component of filmlike myelin sheaths that surround neuron axons.

3 – Imaging mass spectroscopy:This method visualizes substances in tissue sections while retaining their locational information by means of ionization mass spectrometry that directly generates vaporized ions from solid samples.

4 – Ceramide synthase:This enzyme synthesizes ceramide from a sphingoid base and acyl-CoA. Each of the six types of isozymes has substrate specificity towards acyl-CoA with a specific chain length. It is known that ceramide synthase 1 has substrate specificity toward C18 acyl-CoA, and ceramide synthase 2 has substrate specificity toward C22 and C24 acyl-CoAs.