慶應義塾大学 · 生化学・遺伝学・分子生物学
Makoto Suematsu教授の研究室は、代謝プロファイル解析とバイオロジカルガス(CO、NO、H₂Sなど)の機能解明を柱として、肝疾患や血管制御における代謝・シグナル伝達のメカニズムを解明しています。特に、代謝マップのスクリーニングや質量分析を用いた代謝物動態の解析、ならびにヘムを含むタンパク質がガスシグナル伝達に果たす役割を分子構造と機能の観点から解明しています。また、薬物代謝酵素やがんの化学感受性に関与する膜受容体の構造機能解明にも取り組んでいます。
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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