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Mutant of Human Fibroblast Growth Factor-1 (Q40P/S47I/H93G) Has Strong Radioprotective Effects in Mice
https://repo.qst.go.jp/records/70493
https://repo.qst.go.jp/records/70493673b49f6-0669-47d7-be3f-81adcacf9d36
| Item type | 会議発表用資料 / Presentation(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2011-09-05 | |||||
| タイトル | ||||||
| タイトル | Mutant of Human Fibroblast Growth Factor-1 (Q40P/S47I/H93G) Has Strong Radioprotective Effects in Mice | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_c94f | |||||
| 資源タイプ | conference object | |||||
| アクセス権 | ||||||
| アクセス権 | metadata only access | |||||
| アクセス権URI | http://purl.org/coar/access_right/c_14cb | |||||
| 著者 |
Nakayama, Fumiaki
× Nakayama, Fumiaki× Umeda, Sachiko× Asada, Masahiro× Suzuki, Masashi× Zakrzewska, Malgorzata× Imamura, Toru× Imai, Takashi× 中山 文明× 梅田 禎子× 今井 高志 |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | The structural instability of FGF1 limits its potential for practical use, although FGF1 has radioprotective effects. Therefore, we created an FGF1:FGF2 chimera (FGFC) previously and showed that it was structurally more stable than FGF1 and had extremely high radioprotective effects in vivo. In contrast, a number of FGF1 mutants, which were more stable than FGFC, were created. Their rate of cell proliferation increased in order of their structural stability in vitro. The order of stability, from most to least stable, is Q40P/S47I/H93G, Q40P/S47I, other mutants, and FGF1. However, the in vivo contribution of the structural stability of the FGF1 protein to its radioprotective effect remains unknown. This study evaluated and compared the protective activity of FGF1, FGFC and FGF1 mutants in the absence of heparin. Each FGF was administered intraperitoneally to BALB/c mice 24 h before or after total body irradiation (TBI). The su r! viving numbers of crypts per cross-section were determined in the jejunum 3.5 days after TBI. TUNEL assay was performed on paraffin-embedded sections of the jejunum to evaluate apoptosis 24 h after TBI. In the case of administration 24 h before irradiation, both Q40P/S47I/H93G and FGFC had the strongest effect on crypt survival among these FGFs. The radioprotective effect of Q40P was between that of FGF1 and Q40P/S47I/H93G. However, Q40P/S47I increased crypt survival to almost the same extent as FGF1, although it was more stable than Q40P. In addition, Q40P/S47I/H93G and FGFC were effective in promoting crypt survival even when it was administered 24 h after TBI at a dose of 10, 11, or 12 Gy, whereas FGF1 was not effective. Q40P/S47I/H93G or FGFC post-treatment significantly promoted BrdU incorporation into crypts and increased crypt depth, resulting in more epithelial differentiation. In contrast, the number of apoptotic cells in Q40P/S47I/H93G or FGFC-treated mice decreased to alm o! st the same level as that in FGF1-treated mice. These findings showed that Q40P/S47I/H93G enhanced radioprotective activity in vivo to the same extent as FGFC. In contrast, the level of stability of FGF1 did not correlated with that of its protective effect on radiation intestinal damage. Therefore, not only stability but also other conditions might contribute to the radioprotective effect. | |||||
| 会議概要（会議名, 開催地, 会期, 主催者等） | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | 14th International Congress of Radiation Research(ICRR’2011) | |||||
| 発表年月日 | ||||||
| 日付 | 2011-09-01 | |||||
| 日付タイプ | Issued | |||||
