The effect of a proteinase trapping agent, alpha-2-macroglobulin, on the activity of immuno- and neural cells
| Project/Area Number |
04454592
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
機能生物化学
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| Research Institution | Tokyo Institute of Technology |
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Principal Investigator |
IKAI Atsushi Tokyo Inst. of Technology, Bioscience and Biotechnology, professor, 生命理工学部, 教授 (50011713)
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| Co-Investigator(Kenkyū-buntansha) |
ARAKAWA Hideo Tokyo Inst. of Technology, Bioscience and Biotechnology, Assistant, 生命理工学部, 助手 (80211704)
長田 俊哉 東京工業大学, 生命理工学部, 助手 (00201997)
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| Project Period (FY) |
1992 – 1993
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| Project Status |
Completed (Fiscal Year 1993)
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| Budget Amount *help |
¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1993: ¥800,000 (Direct Cost: ¥800,000)
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| Keywords | Alpha-2-macroglubulin / proleaseinhibilor / immvnology / antigen presentation / necrile extension / アルファ-2-マクログロブリン / LRP / 軸索伸展 / α2-マクログロブリン / 抗原提示細胞 / 神経細胞 / ペプチド抗原キャリアー / 軸索伸展活性 |
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| Research Abstract |
Alpha-2-macroglobulin is a varsatile protease inhibitor that can inhibits the activity of a large variety of endoproteinases by a unique mechanism called the trap mechanism. The mechanism assumes that the cleavage of peptide bonds in the "bait region" of alpha-2-M triggers off a gequential intra-molecular reactions that finally causes a global change in the structure of alpha-2-M entrapping the proteinase. Determination of the rate of bait region hydrolysis and those of subsequent reactions including the structural change has been a key lsssue in the study of trap mechanism. In this study we have been successful in determining the rate of bait region cleavage and that of the global structural change for the first time.
As the next accomplishment in this study, we tested our hypothesis that alpha-2-M can be used as an efficient carrier of peptide vaccines to antigen presenting cells such as macrophages. The peptide vaccine concept has been developed to eliminate the hazardous side effects of conventional vaccines derived from bio-materials. Chemically synthesized peptides are used in place of conventlonal vaccines but the low antigenicity of such peptides should be augmented. WE proposed that synthetic peptides can be conjugated to alpha-2-M and administered to host animals. The conjugate can be efficiently taken up by macrophages via receptor mediated endocytosis and eventually activates a high degree of antibody production. The of such experiment in this study has been very promising.
The effect of alpha-2-M the cultured neurons has been examined in this study and the result was positlvely interpreted to show the neurite extension effect of alpha-2-M.The presence of alpha-2-M and its receptor in the brain tissue has been confirmed suggesting the observed activity of the protein could be physiologically important in the brain development.
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Report
(3 results)
Research Products
(26 results)
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[Publications] Mitsuda,S.,Nakagawa,T.,Osada,T.,Shimamoto,T.,Nakazato,H.and Ikai,A.: "A Receptor Mediated Delivery of HIV-1 Derived Peptide Vaccine" Biochem.Biophys.Res.Commun.194. 1155-1160 (1993)
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[Publications] Athauda,S.B.P.,Arakawa,H.,Nishigai,M.,Takahashi,T.,Ikai,A.and Takahashi,K.: "Inhibition of Cathepsin E by α_2-Macroglobulin and the Resulting Structural Changes in the Inhibitor" J.Biochem.113. 526-530 (1993)
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[Publications] Arakawa,H.,Urisaka,T.,Tsuruta,H.,Amemiya,Y.,Kihara,H.and Ikai,A.: "The Kinetics of conformational changes of α_2-macroglobulin determined by time resolved X-ray solution scattering" FEBS Letters. 337. 171-174 (1994)
Description
「研究成果報告書概要(和文)」より
Related Report
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[Publications] Mitsuda, S., Nakagawa, T., Osada, T., Shimamoto, T., Nakazato, H.and Ikai, A.: "A Receptor Mediated Delivery of HIV-1 Derived peptode Vaccine" Biochem. Biophys. Res. Commun.194. 1155-1160 (1993)
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Publications] Atakawa, H., Vrisaka, T., Tsuruta, H., Amemiya, Y., Kihara, H.and Ikai, A.: "The kinetics of conformational changes of alpha2-macro-globulin determined by time resolved X-ray solution scattering" FEBS Letters. 337. 171-174 (1994)
Description
「研究成果報告書概要(欧文)」より
Related Report
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