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    題名: Increased lung uptake of technetium-99m hexamethylpropylene amine oxime in systemic lupus erythematosus
    作者: Shih, CM;Shiau, YC;Wang, JJ;Ho, ST;Kao, A
    貢獻者: 附設醫院核子醫學部;China Med Coll Hosp, Dept Nucl Med, Taichung 404, Taiwan;China Med Coll Hosp, Dept Med Res, Taichung 404, Taiwan;China Med Coll Hosp, Div Pulm & Crit Care Med, Taichung 404, Taiwan;Natl Taiwan Univ, Far Eastern Mem Hosp, Dept Nucl Med, Taipei 10764, Taiwan;Natl Taiwan Univ, Coll Elect Engn, Inst Biomed Engn, Taipei 10764, Taiwan;Chi Mei Med Ctr, Dept Med Res, Tainan, Taiwan;Natl Def Med Ctr, Sch Med, Taipei, Taiwan
    日期: 2002
    上傳時間: 2010-09-24 14:39:14 (UTC+8)
    出版者: KARGER
    摘要: Oligomerization of fibroblast growth factors (FGFs) induced on binding to heparin or heparan sulfate proteoglycan is considered to be crucial for receptor activation and initiation of biological responses. To gain insight into the mechanism of activation of the receptor by FGFs, in the present study we investigate the effect(s) of interaction of a heparin analog, sucrose octasulfate (SOS), on the structure. stability. and biological activities of a recombinant acidic FGF from Notophthalmus viridescens (nFGF-1). SOS is found to bind to nFGF-1 and significantly increase the thermodynamic stability of the protein. Using a variety of technique, such as size-exclusion chromatography, sedimentation velocity, and multidimensional nuclear magnetic resonance (NMR) spectroscopy, it is shown that binding of SOS to nFGF-1 retains the protein in its monomeric state. In its monomeric state (complexed to SOS). n-FGF-1 shows significant cell proliferation activity. N-15 and H-1 chemical shift perturbation and the intermolecular nuclear Overhauser effects (NOEs) between SOS and nFGF-1 reveal that the ligand binds to the dense, positively charged cluster located in the groove enclosed by beta-strands 10 and 11. In addition. molecular modeling based on the NOEs observed for the SOS-nFGF-1 complex. indicates that SOS and heparin share a common binding site on the protein. In conclusion. the results of the present study clearly show that heparin-induced oligomerization of nFGF-1 is not mandatory for its cell proliferation activity.
    關聯: RESPIRATION 69(2):143-147
    顯示於類別:[台中附設醫院] 期刊論文

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