Sugiura, Yuki



School of Medicine, Department of Biochemistry (Shinanomachi)


Assistant Professor/Senior Assistant Professor


Papers 【 Display / hide

  • In situ imaging of monoamine localization and dynamics

    Sugiyama E., Skelly A.N., Suematsu M., Sugiura Y.

    Pharmacology and Therapeutics (Pharmacology and Therapeutics)  208 2020.04

    ISSN  01637258

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    © 2020 Recent advances in sample preparation protocols and instrumentation allow current imaging mass spectrometry (IMS) to enable the visualization of small molecule tissue localization, including that of monoamine neurotransmitters, such as serotonin, dopamine, and norepinephrine. Although monoamine-producing neurons, and their projections and synaptic connections, have been thoroughly characterized, in situ monoamine localization within these circuits remains unclear. Moreover, studying the fluctuations in local monoamine concentration in response to physiological stimuli, drug administration, and neurodegenerative disease progression is worthwhile, and can be achieved by analyzing the in situ concentration maps afforded by coupling IMS with on-tissue derivatization protocols. Recent reports have shown that monoamines localize within cell bodies and also translocate to distant nerve terminals, indicating active transport along axons and/or local synthesis at the terminals. Moreover, IMS can reveal regionally segregated monoamine fluctuations, such as rapid dopamine fluctuation within the nucleus accumbens (NAc) subregion during pain sensation. Furthermore, since exogenous drug pharmacokinetics can also be visualized by IMS, this technique could provide powerful methodologies enabling the simultaneous imaging of monoamines and drugs that selectively regulate monoamine signaling, such as serotonin reuptake inhibitors (SSRIs). Therefore, IMS could reveal where SSRIs administered over the long-term accumulate and how they affect local monoamine metabolism.

  • Quantitative MALDI-MS/MS assay for serum cortisol through charged derivatization

    Nakamura M., Moritsuna M., Yuda K., Fujimura S., Sugiura Y., Shimma S., Nishimoto K., Nishikawa T., Suematsu M., Ogawa S., Higashi T.

    Journal of Pharmaceutical and Biomedical Analysis (Journal of Pharmaceutical and Biomedical Analysis)  178 2020.01

    ISSN  07317085

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    © 2019 Elsevier B.V. Cortisol (CRT), the main glucocorticoid in humans, plays a crucial role in many physiological processes, therefore, the measurement of its serum level is of great clinical significance. Matrix-assisted laser desorption/ionization-tandem mass spectrometry (MALDI-MS/MS) might be an effective approach for the quantification of CRT in serum due to its attractive properties, i.e., high specificity, ease of use, ruggedness and rapid analysis. In this study, we developed a method to quantify the serum CRT by MALDI-MS/MS. This method employed the derivatization using a Girard-type reagent, 1-(hydrazinocarbonylmethyl)isoquinolinium chloride, which compensated for the lack of sensitivity. This method enabled the reproducible quantification of the serum CRT using a 20-μL sample (intra- and inter-assay relative standard deviations, 7.4% or lower), and the measurable range was 25–500 ng/mL. The serum CRT concentrations determined by the newly-developed MALDI-MS/MS method agreed well with those by liquid chromatography/electrospray ionization-MS/MS or electrochemiluminescence immunoassay. The MALDI-MS/MS method was used for the analysis of peripheral venous serum samples of healthy subjects and adrenal venous serum samples of patients with primary aldosteronism, and satisfactory results were obtained.

  • Loss of autophagy impairs physiological steatosis by accumulation of NCoR1

    Takahashi S.s., Sou Y.S., Saito T., Kuma A., Yabe T., Sugiura Y., Lee H.C., Suematsu M., Yokomizo T., Koike M., Terai S., Mizushima N., Waguri S., Komatsu M.

    Life Science Alliance (Life Science Alliance)  3 ( 1 )  2020

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    © 2019 Takahashi et al. Lipid droplets (LDs) are dynamic organelles that store neutral lipids during times of energy excess, such as after a meal. LDs serve as an energy reservoir during fasting and have a buffering capacity that prevents lipotoxicity. Autophagy and the autophagic machinery have been proposed to play a role in LD biogenesis, but the underlying molecular mechanism remains unclear. Here, we show that when nuclear receptor co-repressor 1 (NCoR1), which inhibits the transactivation of nuclear receptors, accumulates because of autophagy suppression, LDs decrease in size and number. Ablation of ATG7, a gene essential for autophagy, suppressed the expression of gene targets of liver X receptor α, a nuclear receptor responsible for fatty acid and triglyceride synthesis in an NCoR1-dependent manner. LD accumulation in response to fasting and after hepatectomy was hampered by the suppression of autophagy. These results suggest that autophagy controls physiological hepatosteatosis by fine-tuning NCoR1 protein levels.

  • A thin layer of sucrose octasulfate protects the oesophageal mucosal epithelium in reflux oesophagitis

    Hayakawa T., Kawasaki S., Hirayama Y., Tsutsui T., Sugiyama E., Adachi K., Kon R., Suematsu M., Sugiura Y.

    Scientific Reports (Scientific Reports)  9 ( 1 )  2019.12

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    © 2019, The Author(s). Sucralfate is effective for the treatment of gastric and duodenal ulcers owing to its protective gel-forming ability. However, the mechanism by which sucralfate protects the oesophageal mucosa against reflux oesophagitis has not been clarified. We aimed to investigate the mechanisms of action of sucralfate and sucrose octasulfate (SOS), a component of sucralfate. SOS and sucralfate were administered to oesophagitis-induced rats, and the ulcer lesion size was macroscopically examined and scored. Effective pepsin activity in the gastric juices obtained from the animal model was evaluated by a casein digestion test. Sucralfate and SOS improved the pathology scores in a dose-dependent manner, whereas gastric juice pepsin activity was not impaired by therapeutic doses of SOS. As SOS lacks the ability to form a thick gel layer by polymerisation, we examined the distribution of SOS in the mucosal lumen by imaging mass spectrometry (IMS) to determine whether SOS directly adheres to the mucosal surface. A clear homogeneous thin-layer SOS film (>100 μm thick) was visualized on the oesophageal mucosal surface. Moreover, this SOS film formation was enhanced at ulcer lesion sites. Taken together, SOS appears to protect oesophageal mucosa against reflux oesophagitis via thin-layer formation on the mucosal surface.

  • Autophagy regulates lipid metabolism through selective turnover of NCoR1

    Saito T., Kuma A., Sugiura Y., Ichimura Y., Obata M., Kitamura H., Okuda S., Lee H., Ikeda K., Kanegae Y., Saito I., Auwerx J., Motohashi H., Suematsu M., Soga T., Yokomizo T., Waguri S., Mizushima N., Komatsu M.

    Nature Communications (Nature Communications)  10 ( 1 )  2019.12

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    © 2019, The Author(s). Selective autophagy ensures the removal of specific soluble proteins, protein aggregates, damaged mitochondria, and invasive bacteria from cells. Defective autophagy has been directly linked to metabolic disorders. However how selective autophagy regulates metabolism remains largely uncharacterized. Here we show that a deficiency in selective autophagy is associated with suppression of lipid oxidation. Hepatic loss of Atg7 or Atg5 significantly impairs the production of ketone bodies upon fasting, due to decreased expression of enzymes involved in β-oxidation following suppression of transactivation by PPARα. Mechanistically, nuclear receptor co-repressor 1 (NCoR1), which interacts with PPARα to suppress its transactivation, binds to the autophagosomal GABARAP family proteins and is degraded by autophagy. Consequently, loss of autophagy causes accumulation of NCoR1, suppressing PPARα activity and resulting in impaired lipid oxidation. These results suggest that autophagy contributes to PPARα activation upon fasting by promoting degradation of NCoR1 and thus regulates β-oxidation and ketone bodies production.

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Papers, etc., Registered in KOARA 【 Display / hide

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Research Projects of Competitive Funds, etc. 【 Display / hide

  • 網羅的な神経伝達物質の可視化法開発と精神疾患研究への適用


    MEXT,JSPS, Grant-in-Aid for Scientific Research, 杉浦 悠毅, Grant-in-Aid for Young Scientists (A), Principal Investigator

  • Visualization and quantification of fluxes of glucose metabolic pathways in brain


    MEXT,JSPS, Grant-in-Aid for Scientific Research, 杉浦 悠毅, Grant-in-Aid for Challenging Exploratory Research, Principal Investigator

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    In response to a stimuli, neurons and astrocytes alter their metabolic pathways to fit their elevated energy demands. For example, it is known that a stimulation to an animal increase the amount of glucose consumption in the brain region specific manner. To understand molecular mechanism of this phenomenon, a molecular imaging approach is effective. In this research, we developed the novel flux analysis using stable isotopes in combination with MALDI- imaging mass spectrometry, as well as quantitative metabolomics. Those lead us to answer the questions including “during a neural stimulation, in what anatomical regions of the brain, is which metabolic derangement occurring?”. We finally identified a novel metabolic mediator shuttled between neurons and astrocytes up on the stimulation.


Courses Taught 【 Display / hide