Keio University · Biochemistry, Genetics and Molecular Biology
Professor Makoto Suematsu's research lab specializes in gasotransmitter biology and redox signaling, focusing on the roles of gaseous signaling molecules such as carbon monoxide (CO), nitric oxide (NO), and hydrogen sulfide (H2S) in physiological and pathological processes. The lab investigates the molecular mechanisms of heme-based proteins in gas generation, sensing, and signaling, particularly in vascular and metabolic regulation. Using advanced analytical techniques like capillary electrophoresis-time-of-flight mass spectrometry and crystallography, the lab explores how these gaseous mediators influence cellular metabolism, liver function, and disease progression, including hepatotoxicity and cancer. Their work bridges systems biology, metabolomics, and structural biology to uncover novel regulatory pathways in health and disease.
Figures are computed from collected data and may differ slightly.
Metabolomics is an emerging tool that can be used to gain insights into cellular and physiological responses. Here we present a metabolome differential display method based on capillary electrophoresis time-of-flight mass spectrometry to profile liver metabolites following acetaminophen-induced hepatotoxicity. We globally detected 1,859 peaks in mouse liver extracts and highlighted multiple changes in metabolite levels, including an activation of the ophthalmate biosynthesis pathway. We confirme
Heme oxygenase is a heme-oxidizing enzyme which generates biliverdin and carbon monoxide (CO). The present study was designed to elucidate whether CO endogenously produced by this enzyme serves as an active vasorelaxant in the hepatic microcirculation. Microvasculature of the isolated perfused rat liver was visualized by dual-color digital microfluorography to alternately monitor sinusoidal lining and fat-storing Ito cells. In the control liver, the CO flux in the venous effluent ranged at 0.7 n
The diverse physiological actions of the "biologic gases," O2, CO, NO, and H2S, have attracted much interest. Initially viewed as toxic substances, CO, NO, and H2S play important roles as signaling molecules. The multiplicity of gas actions and gas targets and the difficulty in measuring local gas concentrations obscures detailed mechanisms whereby gases exert their actions, and many questions remain unanswered. It is now readily apparent, however, that heme-based proteins play central roles in
Progesterone-receptor membrane component 1 (PGRMC1/Sigma-2 receptor) is a haem-containing protein that interacts with epidermal growth factor receptor (EGFR) and cytochromes P450 to regulate cancer proliferation and chemoresistance; its structural basis remains unknown. Here crystallographic analyses of the PGRMC1 cytosolic domain at 1.95 Å resolution reveal that it forms a stable dimer through stacking interactions of two protruding haem molecules. The haem iron is five-coordinated by Tyr113, a
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