Discovery of novel sulfated bioregulatory molecules acting on neural tissue receptors
Project/Area Number |
15H04502
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Food science
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Research Institution | University of Miyazaki |
Principal Investigator |
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Co-Investigator(Kenkyū-buntansha) |
水光 正仁 宮崎大学, 理事・副学長 (00128357)
榊原 啓之 宮崎大学, 農学部, 教授 (20403701)
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Project Period (FY) |
2015-04-01 – 2019-03-31
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Project Status |
Completed (Fiscal Year 2018)
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Budget Amount *help |
¥16,770,000 (Direct Cost: ¥12,900,000、Indirect Cost: ¥3,870,000)
Fiscal Year 2018: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2017: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2016: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2015: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
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Keywords | 硫酸転移酵素 / 硫酸化 / レセプター / 生体制御分子 / sulfation / sulfotransferase / sulfated / GPCR / 生体制御分子硫酸体 / 神経 |
Outline of Final Research Achievements |
In this study, we focused on the functional control of bioregulatory molecules by sulfation as a metabolic mechanism. First, enzymatic preparation method of sulfated bioregulatory molecules were developed. Furthermore, we conducted research aimed at developing analysis technology for cell surface receptor-mediated signal transduction and elucidating its physiological function in cultured cells. Specifically, using E. coli that expressing human cytosolic sulfotransferase, we have established a biotechnology method to prepare a sulfated metabolite of a bioregulatory molecules such as food components. The obtained sulfated metabolite confirmed the chemical structure by NMR. Furthermore, a luciferase assay to evaluate GPR30 receptor-mediated activity was established, and the sulfated metabolites were evaluated for functional analysis.
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Academic Significance and Societal Importance of the Research Achievements |
現在、市場に流通する医薬品のほとんどがGタンパク質共役受容体を介して作用すると言われ、生体制御分子(ホルモン、食品機能性成分、医薬品など)の多くが受容体を標的として作用する。さらに、これら生体制御分子の多くは、肝臓等で代謝され、その代謝産物が神経細胞などで受容体に作用し機能していることが想定される。本研究は、硫酸化を受けた代謝物が受容体を介して細胞に作用することを確認した。このことは、硫酸化された代謝物は不活性な状態として排泄されているという定説を覆す知見となる。さらに、硫酸化代謝物に新規機能性を開発することで医薬品等の候補分子としての優位性を示すことが可能となる。
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Report
(5 results)
Research Products
(57 results)
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[Journal Article] Effects of human sulfotransferase 2A1 genetic polymorphisms 3 on the sulfation of Tibolone.2018
Author(s)
Miller, E., Zalzala, M.H., Abunnaja, M.S, Kurogi, K., Sakakibara, Y., Suiko, M., Liu, M.-C.
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Journal Title
European Journal of Drug Metabolism and Pharmacokinetics
Volume: -
Issue: 4
Pages: 415-421
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Sulfation of catecholamines and serotonin by SULT1A3 allozymes.2018
Author(s)
Bairam, A.F., Rasool, M.I., Alherz, F.A., Abunnaja, M.S., El Daibani, A.A., Gohal, S.A., Kurogi, K., Sakakibara, Y., Suiko, M., Liu, M.-C.
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Journal Title
Biochamical Pharmacology
Volume: 151
Pages: 104-113
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Radical scavenging effects of 1-naphthol, 2-naphthol, and their sulfate-conjugates2018
Author(s)
Sugahara S, Fukuhara K, Tokunaga Y, Tsutsumi S, Ueda Y, Ono M, Kurogi K, Sakakibara Y, Suiko M, Liu M-C, Yasuda S.
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Journal Title
The Journal of Toxicological Sciences
Volume: 43
Issue: 3
Pages: 213-221
DOI
NAID
ISSN
0388-1350, 1880-3989
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Effects of genetic polymorphisms on the sulfation of dehydroepiandrosterone and pregnenolone by human cytosolic sulfotransferase SULT2A12018
Author(s)
Abunnaja, M.S., Alherz, F.A., El, Daibani, A.A., Bairam, A.F., Rasool, M.I., Gohal, S.A., Kurogi, K., Sakakibara, Y., Suiko, M., Liu, M.-C.
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Journal Title
Biochemistry and Cell Biology
Volume: 96
Issue: 5
Pages: 655-662
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] The critical role of His48 in mouse cytosolic sulfotransferase SULT2A8 for the 7alfa-hydroxyl sulfation of bile acids2018
Author(s)
Shimohira, T., Kurogi, K., Liu, M.-C., Suiko, M., Sakakibara, Y.
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Journal Title
Bioscience, Biotechnology, and Biochemistry
Volume: 82
Issue: 8
Pages: 1359-136
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] On the role of genetic polymorphisms in the cholesterol by human cytosolic sulphotransferase SULT2B1b2018
Author(s)
Alherz, F.A., Daibani, A.A., Bairam, A.F., Abunnaja, M.S., El, Rasool, M.I., Kurogi, K., Sakakibara, Y., Suiko, M., Liu, M.-C.
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Journal Title
Journal of Biochemistry
Volume: 164
Issue: 3
Pages: 215-221
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Identification of zebrafish steroid sulfatase and comparative analysis of the enzymatic properties with human steroid sulfatase2018
Author(s)
Kurogi, K., Yoshihama, M., Williams, F.E., Kenmochi, N., Sakakibara, Y., Suiko, M., Liu, M.-C.
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Journal Title
The Journal of Steroid Biochemistry and Molecular Biology
Volume: 185
Pages: 110-117
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Identification and characterization of the zebrafish glutathione S-transferase Pi-1.2017
Author(s)
Abunnaja, M. S., Kurogi, K., Mohammed, Y. I., Sakakibara, Y., Suiko, M., Hassoun, E., Liu, M.-C.
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Journal Title
Journal of Biochemical and Molecular Toxicology
Volume: 31
Issue: 10
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Δ4-3-Ketosteroids as a new class of substrates for the cytosolic sulfotransferases.2017
Author(s)
Hashiguchi, T., Kurogi, K., Shimohira, T., Teramoto, T., Liu, M.-C., Suiko, M., Sakakibara, Y.10.1016/j.bbagen.2017.08.005.
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Journal Title
Biochimica et Biophysica Acta
Volume: 1861
Issue: 11
Pages: 2883-2890
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Identification and characterization of 5alpha-cyprinol-sulfating cytosolic sulfotransferases (Sults) in the Zebrafish (Danio rerio).2017
Author(s)
Kurogi, K., Yoshihama, M., Horton, A., Schiefer, I.T., Krasowski, M.D., Hagey, L.R., Williams, F.E., Sakakibara, Y., Kenmochi, N., Suiko, M., Liu, M.-C.
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Journal Title
The Journal of Steroid Biochemistry and Molecular Biology
Volume: 174
Pages: 120-127
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Structural basis for the broad substrate specificity of the human tyrosylprotein sulfotaransferase-1.2017
Author(s)
Tanaka, S., Nishiyori, T., Kojo, H., Otsubo, R., Tsuruta, M., Kurogi, K., Liu, M.-C., Suiko, M., Sakakibara, Y., Kakuta, Y.
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Journal Title
Scientific Reports
Volume: 7
Issue: 1
Pages: 8776-8776
DOI
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Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Human cytosolic sulphotransferase SULT1C3: genomic analysis and functional characterization of splice variant SULT1C3 and SULT1C3d.2017
Author(s)
Kurogi, K., Shimohira, T., Kouriki-Nagatomo, H., Zhang, G., Miller, E.R., Sakakibara, Y., Suiko, M., Liu, M.-C.
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Journal Title
Journal of Biochemistry
Volume: 162
Issue: 6
Pages: 403-414
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Regioselective production of sulfated polyphenols using human cytosolic sulfotransferase (SULT)-expressing Escherichia coli cells.2017
Author(s)
Shimohira, T., Kurogi, K., Hashiguchi, T., Liu, M.-C., Suiko, M., Sakakibara, Y.
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Journal Title
J. Biosci. Bioeng.
Volume: -
Issue: 1
Pages: 84-90
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] A substrate-bound structure of cyanobacterial biliverdin reductase identifies stacked substrates as critical for activity2017
Author(s)
Haruna Takao, Kei Hirabayashi, Yuki Nishigaya, Haruna Kouriki, Tetsuko Nakaniwa, Yoshinori Hagiwara, Jiro Harada, Hideaki Sato, Toshimasa Yamazaki, Yoichi Sakakibara, Masahito Suiko, Yujiro Asada, Yasuhiro Takahashi, Ken Yamamoto, Keiichi Fukuyama, Masakazu Sugishima, and Kei Wada
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Journal Title
Nat. Commun.
Volume: 8
Issue: 1
Pages: 1-10
DOI
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Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Human Cytosolic Sulfotransferase SULT1A3 Mediates the Sulfation of Dextrorphan2016
Author(s)
Yamamoto, A., Kurogi, K., Schiefer, I.T., Liu, M.-Y., Sakakibara, Y., Suiko, M., Liu, M.-C.
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Journal Title
Biological and Pharmaceutical Bulletin
Volume: 39
Issue: 9
Pages: 1432-1436
DOI
NAID
ISSN
0918-6158, 1347-5215
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Identification and Characterization of the Human Cytosolic Sulfotransferases Mediating the Sulfation of Clioquinol and Iodoquinol2016
Author(s)
Yamamoto, A., Debrah-Pinamang, M., DiModica, N.J., Kurogi, K., Naqvi, A.A., Hui, Y., Sakakibara, Y., Suiko, M., Liu, M.-C.
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Journal Title
Drug Metab. Lett.
Volume: 10
Pages: 200-205
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] A novel procedure for the assessment of the antioxidant capacity of food components.2016
Author(s)
Yoshimura, T., Harashima, M., Kurogi, K., Suiko, M., Liu, M.-C., Sakakibara, Y.
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Journal Title
Anal. Biochem.
Volume: 507
Pages: 7-12
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Sulfate Conjugation of Daphnetin by the Human Cytosolic Sulfotransferases.2016
Author(s)
Han, Z., Xi, Y., Luo, L., Zhou, C., Kurogi, K., Sakakibara, Y., Suiko, M., Liu, M.-C.
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Journal Title
J. Ethnopharmacol.
Volume: S0378-8741
Pages: 30311-30317
DOI
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Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Sulfation of Acetaminophen by the Human Cytosolic Sulfotransferases: A Systematic Analysis.2015
Author(s)
Yamamoto, A., Liu, M.-Y., Kurogi, K., Sakakibara, Y., Saeki, Y., Suiko, M., Liu, M.-C.
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Journal Title
The Journal of Biochemistry
Volume: 158
Pages: 497-504
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Sulfation of afimoxifene, endoxifen, raloxifene, and fulvestran by the human cytosolic sulfotransferases (SULTs): A system analysis.2015
Author(s)
Hui, Y., Luo, L., Zhang, L., Kurogi, K., Zhou, C., Sakakibara, Y., Suiko, M., Liu, M.-C.
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Journal Title
Journal of Pharmacological Sciences
Volume: 128
Issue: 3
Pages: 144-149
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Sulfation of 6-Gingerol by the Human Cytosolic Sulfotransferases: A Systematic Analysis.2015
Author(s)
Luo, Y., Mei, X., Xi, Y., Zhou, C., Hui, Y., Kurogi, K., Sakakibara, Y., Suiko, M., Liu, M.-C.
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Journal Title
Planta Medica
Volume: 82
Issue: 03
Pages: 238-243
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Sulfation of 6-hydroxymelatonin, N-acetylserotonin and 4-hydroxyramelteon by the human cytosolic sulfotransferases (SULTs)2015
Author(s)
Luo, L., Zhou, C., Kurogi, K., Sakakibara, Y., Suiko, M., Liu, M.-C.
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Journal Title
Xenobiotica
Volume: 46
Issue: 7
Pages: 612-619
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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