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Studies on the mechanisms of the anti-inflammatory and anti-viral native substances

Research Project

Project/Area Number 08670532
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 内科学一般
Research InstitutionKitasato University

Principal Investigator

OHTSUKI Kenzo  Professor, Dept.of Molecular Biochem.School of Allied Health Sciences, Kitasato University, 医療衛生学部, 教授 (60124559)

Co-Investigator(Kenkyū-buntansha) KAWAGUCHI Kiichiro  Lecture, Dept.of Pharmacology, School of Pharmaceutical Sciences, Kitasato Unive, 薬学部, 講師 (10146334)
TANAKA Yuetsu  Associate Professor, Det.of Immunology, School of Sciences, Kitasato University, 理学部, 助教授 (30163588)
Project Period (FY) 1996 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1997: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1996: ¥1,400,000 (Direct Cost: ¥1,400,000)
KeywordsMolecular mechanism / Anti-viral effect / Anti-inflammatory effect / Natural substance / Specific receptor / Protein kinase / Signal transduction / Gene expression / 天然薬物 / 特異受容体 / 抗炎症作用 / 抗ウイルス作用 / プロテインキナーゼ
Research Abstract

The project study was done to investigate (i) purification of the specific binding proteins (gbPs) of anti-inflammatory egent, glycyrrhizin, from GL-sensitive mammalian cells, (ii) identification of gbPs by determination of their N-terminal partial amino acid sequences, and (iii) kinetics of the GL-induced selective inhibition of their physiological activities in vitro.
To purify the gbPs from GL-sensitive mammalian cells or mouse tissues (liver and spleen) , a GL-affinity column was prepared. By using this GL-affinity column, several gbPs were purified to homogenous polypeptides after partial purification of the 1.5 M NaC1 clude extracts by combination with CM-cellulose column cromatography and gel filtration on a Superdex 200pg column (HPLC) . Determination of their N-termina partial amino acid sequences revealed that (i) arachidonate cascade enzymes, such as phospholipase A_2 (PLA_2) , 5'-1ipoxygenase (5'-LOX) and lipocortin I,are identified as gbPs ; (ii) serine protease (p32) , hyaluronidase (p55) comperiment C3 and immunoglobulin (Igg) are identified as gbPs in human serum ; and (iii) 14 kDa secetory PLA_2 (14 kDa sPLA_2 ) and serine protease are identified as gbPs in the synovial fluids of patients with rheumatonoid arthritis. Furthermore, kenitic studies revealed that GL,but not GA,at low levels (1-5muM) inhibits the-physiological activities of these gbPs and also selectively inhibits the CK-II-mediated activation of these gbPs in vitro.

Report

(3 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • 1996 Annual Research Report
  • Research Products

    (28 results)

All Other

All Publications (28 results)

  • [Publications] Ohtsuki, K, Nishikawa, Y., Saito, H., Munakata, H.and Kato.T.: "DNA-binding proteins with oligo-arginine clusters function as potent activators for CK-II in vitro" FEBS Letters. 378. 115-120 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Harada, S., Karino, A., Shimoyama, Y.Shamsa, F.and Ohtsuki, K.: "Identification of glycyrrhizin-binding protein kinase as casein kinase II and characterization of its associated phosopgate acceptors in mouse liver" Biochem.Biophys.Res.Commun.227. 102-109 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Shimoyama, S., Ohtaka, H., Nagata, N.Munakata, H., Hayashi, N.and Ohtsuki, K.: "Physiological correlation between glycyrrhizin,glycyrrhizin-binding lipoxygenase and casein kinase II" FEBS Letters. 391. 238-242 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Karino, K., Nakamura, T.and Ohtsuki, K.: "The inhibitory effect of actin on casein II activity in vitro" FEBS Letters. 398. 317-321 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Furuya, T., Shimoyama, S., Nagata, N.and Ohtsuki, K.: "Biochemical characterization of selective inhibitors for a glycyrrhizin-binding lipoxygenase from soybeans" Biosoi.Biotech.Biochem.61. 495-500 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Furuka, T., Yamagata, S., Morishima, N.and Ohtsuki, K.: "Biochemical characterization of glycyrrhizin as an effective inhibitor for hyaluronidases from bovine testis" Biol.Pharm.Bull.20. 973-977 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Ohtsuki, K.and Ono, Y.: "Neocarzinostatin(NCS):past,present and future developments" Springer-Verlag Tokyo (分担執筆), 129-154 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Ohtsuk, K., Nishikaw, Y., Saito, H., Munakat, H.and Kat, T.: "DNA-binding protein with oligo-arginine clusters function as potent activators for CK-II in vitro" FEBS Letters. 378. 115-120 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Harada, S., Karino, A., Shimoyama, Y., Shamsa, F.and Ohtsuki, K.: "Identification of glycyrrhizin-binding protein kinase as casein kinase II and characterization of its associated phosphate acceptors in mouse liver." Biochem. Biophys. Res. Commun.227. 102-109 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Shimoyama, S., Ohtaka, H., Nagata, N., Munakata, H., Hayashi, N.and Ohtsuki, K.: "Physiological correlation between glycyrrhizin, glycyrrhizin-binding lipoxygenase and casein kinase II" FEBS Letters. 391. 238-242 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Karino, K., Nakamur, T.and Ohtsuki, K.: "The inhibitory effect of actin on casein kinase II activity in vitro." FEBS Letters. 398. 317-321 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Furuya, T., Shimoyama, S., Nagata, N.and Ohtsuki, K.: "Biochemical characterization of selective inhibitors for a glycyrrhizin-binding lipoxygenase from soybeans" Biosoi.Biotech.Biochem.61(3). 495-500 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Furuka, T., Yamagata, S., Morishima, N.and Ohtsuki, K.: "Biochemical characterization of glycyrrhizin as an effective inhibitor for hyaluronidases from bovine testis." Biol.Pharm.Bull.20. 973-977 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Tanoue, S., Karino, A., Nayuki, S.and Ohtsuki, K.: "Neocarzinostatin-chromophore : a potent inhibitor of casein kinase II in vitro." J.Antibiotics. 51(1). 95-97 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Ohtsuki, K., Abe, W., Shimoyama, Y., Furuya, T., Munakata, H.and Takachika, Y.: "Separation of phospholipases A_2 in habu snake venom by glycyrrhizin (GL) -affinity column chromatography and identifiction of a GL-sensitive enzyme." Biol.Pharm.Bull.20(6)(in press). (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Ohtsuki, K., Maekawa, T., Harada, S., Karino, A., Morikawa, Y.and Ito, M.: "Biochemical characterization of HIV-1 Rev as a potent activator of casein kinase II in vitro." FEBS Letters. 427 (in press). (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Ohtsuki, K.and Harad, S.: "The biochemical mechanisms involved in the anti-inflammatory effect of glycyrrhizin" Minopha.Med.Rev.42(2). 55-62 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Ohtsuki, K.and Ono, Y.: The biochemical mechanisms involved in the biological effects induced by neocarzinostatin (NCS) and the NCS-chromophore.(ed.by Maeda, H., Edo, K.and Ishida, N.). Springer-Verlag Tokyo, 129-154 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Furuya,T.et al.: "Biochemical characterization of glycyrrhizin as an effective inhibitor for hyaluronidases from bovine testis." Biol.Pharm.Bull.20・9. 973-977 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Tanoue,S.et al.: "Neocarzinostatin-chromophore:a potent inhibitor of casein kinase II in vitro." J.Antibiotics. 51・1. 95-97 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Ohtsuki,K.et al.: "Separation of phospholipase A2 in habu snake venom by glycyrrhzin(GL)-affinity column chromatography and identification of a GL-sensitive enzyme." Biol.Pharm.Bull.21・6. 1230-1236 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Tanaka Y.,et al.: "Productive and lytic infection of human CD^<4+> type 1 helper T cells with macrophage-tropic human immunodeficiency virus type 1." J.Virol.71. 465-470 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Shimoyama,Y.: "physiological correlation between glycurrhizin,Glycyrnhizin-binding lipoxygenase and casein kinase II" FEBS Letters. 391. 238-242 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Karino,A.: "Au inhibitory effect of actin on casein kinase II activity in vitro" FEBS Letters. 398. 317-321 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Harada,S.: "Identification of glycyrnhizin-binding protein kinase as CK-II and characterization of its associated phosphate acceptors in mouse liver" Biochem.Biophys.Res.Commun.227. 102-109 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Furuya,T.: "Biochemical characteization of selective inhibitors for a glycyrnhizin-binding lopoxygenase from soybeaus" Biosci.Biotech.Biochem.61・3. 495-500 (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] 大槻健蔵: "グリチルリチン(GL)の抗炎症作用機構" Minophageu Medical Review. 42・2. 55-62 (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] 大槻健蔵: "NCS-chromophoreによるDNA切断機構" 生化学. 68・12. 1817-1824 (1996)

    • Related Report
      1996 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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