Visualization of oxygenase producing bioactive metabolites by mass spectrometry imaging

 

Yuki Sugiura

Center for Cancer Immunotherapy and Immunobiology, Kyoto University School of Medicine

 

Small signaling molecules such as NO, CO, monoamines, prostaglandins, and steroid hormones orchestrate the programmed progression and resolution of inflammation. It must be noted once again that all of these small molecules found by classical biochemical studies are produced by molecular oxygenation reactions catalyzed by oxygenases.

 

 

Although the in vitro bioactivity of these small molecule signal mediators has been well studied, their in vivo spatiotemporal kinetics (i.e., in which cells they are produced, diffused, and degraded) is not well understood due to the lack of effective molecular imaging techniques. We have developed a highly sensitive imaging mass spectrometry (IMS) to fill this technological gap. In recent years, the tissue localization of monoamines and steroid hormones has been visualized, enabling the identification of novel serotonin and aldosterone producing cells.

 

 

 

Here, I’ll introduce more recent progress in the development of IMS technology and its applications. First, by visualizing the dynamics of the neurotransmitter serotonin throughout the body, we show how activation of immune cells alters monoamine metabolism in the brain, ultimately causing behavioral changes in animals with strong inflammation (Nature immunology 18 (12), 1342-1352.75. 2017). Next, the GABA signaling network between immune cells, discovered by visualizing the microenvironment of small molecule signaling (GABA) in tumor resection specimens from patients, will also be presented (Nature 599 (7885), 471-476.2021).

 

I hope that participants will be interested in the in vivo metabolic biochemistry opened up by cutting-edge IMS and metabolomics analysis.