Difference in physiological roles of phosphorylated and non-phosphorylated rat fetuin.
磷酸化和非磷酸化大鼠胎球蛋白生理作用的差异。
基本信息
- 批准号:06454524
- 负责人:
- 金额:$ 4.61万
- 依托单位:
- 依托单位国家:日本
- 项目类别:Grant-in-Aid for General Scientific Research (B)
- 财政年份:1994
- 资助国家:日本
- 起止时间:1994 至 1995
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
In this project, we obtained following results.1. Rat fetuin synthesized and secreted by hepatocytes was phosphorylated form and the rate of biosynthesis of this phosphorylated fetuin (phosphofetuin) was suppressed by inflammatory cytokines such as IL-1 (alpha and beta) and TNF-alpha, but it was stimulated by growth factors to hepatocytes such as hepatocyte growth factor (HGF), epidermal growth factor and insulin. This regulation of biosynthesis of phosphofetuin was confirmed both by the levels of protein and mRNA.2. Phosphofetuin suppressed the biological activity of HGF which is known to be a potent mitogen to hepatocytes. However, non-phosphorylated fetuin did not show the activity to suppress the HGF activity. For the mechanism how phosphofetuin suppress the HGF activity, we found that phosphofetuin has affinity to bound HGF and thus phosphofetuin interfered with HGF binding to its specific receptor, c-Met. These observation suggest that phosphofetuin synthesized by hepatocytes may be a natural modulator of HGF as a 7chalone'.3. Non-phosphorylated rat fetuin enhanced bone resorption induced by low concentrations (0.1-0.5nM) of parathyroid hormone (PTH), as measured by release of ^<45>Ca from ^<45>Ca-prelabeled rat radius, but it had no activity on bone resorption without PTH.We also found that rat non-phosphorylated fetuin enhanced the digestion of type I collagen by cathepsin L.4. Although bovine fetuin and its human counterpart of alpha_2-HS glycoprotein is known to be a plasma sialoprotein for long time, its physiological role is not yet clear. From above observations using rat fetuin, we found one of physiological roles of phosphorylated and non-phosphorylated fetuin/alpha_2-HS glycoprotein.
在这个项目中,我们得到了以下结果:肝细胞合成和分泌的大鼠胎蛋白以磷酸化形式存在,磷酸化后的胎蛋白(phosphofetuin)的生物合成速率受到IL-1 (α和β)和tnf - α等炎性细胞因子的抑制,但受到肝细胞生长因子(HGF)、表皮生长因子和胰岛素等生长因子的刺激。蛋白和mrna水平证实了这种对磷蛋白生物合成的调节。磷蛋白抑制HGF的生物活性,HGF是肝细胞的一种有效的丝裂原。而非磷酸化胎蛋白对HGF活性无抑制作用。对于磷蛋白抑制HGF活性的机制,我们发现磷蛋白与HGF具有亲和力,从而干扰了HGF与其特异性受体c-Met的结合。这些观察结果表明,肝细胞合成的卵黄蛋白可能是HGF的天然调节剂。非磷酸化大鼠胎儿素增强低浓度(0.1-0.5nM)甲状旁腺激素(PTH)诱导的骨吸收,通过^<45>Ca预标记的大鼠桡骨释放^<45>Ca来测量,但对没有PTH的骨吸收没有活性。我们还发现,大鼠非磷酸化的胎儿素增强了组织蛋白酶L.4对I型胶原的消化。虽然很早以前就知道牛胎蛋白和人α _2- hs糖蛋白是一种血浆唾液蛋白,但其生理作用尚不清楚。通过对大鼠胎蛋白的上述观察,我们发现了磷酸化和非磷酸化的胎蛋白/alpha_2-HS糖蛋白的生理作用之一。
项目成果
期刊论文数量(26)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Y.Daikuhara: Liver diseases and hepatocyte growth factor. Liver Diseases and Growth Factor (T.Kuroki, ed.). Medical View, Tokyo, 136-150 (1995)
Y.Daikuhara:肝脏疾病和肝细胞生长因子。
- DOI:
- 发表时间:
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- 影响因子:0
- 作者:
- 通讯作者:
T.Ohnishi, et al.: "Effects of cytokines and growth factors on phosphorylated fetuin biosynthesis by adult rat hepatocytes in primary culture." Biochem. Biophys. Res. Commun.200. 598-605 (1994)
T.Ohnishi 等人:“细胞因子和生长因子对原代培养中成年大鼠肝细胞磷酸化胎球蛋白生物合成的影响”。
- DOI:
- 发表时间:
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- 影响因子:0
- 作者:
- 通讯作者:
Sakaguchi,H.: "Ultrastructural location of human hepatocyte growth factor in human liver" Hepatology. 19. 1157-1163 (1994)
Sakaguchi,H.:“人肝细胞生长因子在人肝脏中的超微结构定位”肝病学。
- DOI:
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- 影响因子:0
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大工原 恭: "ヒト肝細胞増殖因子の発現と臨床的意義" 日本臨床化学会雑誌. (印刷中). (1995)
Kyo Daikuhara:“人肝细胞生长因子的表达和临床意义”,日本临床化学学会杂志(1995 年出版)。
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- 影响因子:0
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大工原恭(分担): "肝疾患と肝細胞増殖因子(肝疾患と細胞増殖因子、黒木登志夫編)" メジカルレビュー社, 136-150 (1995)
Kyo Daikuhara(撰稿人):“肝脏疾病和肝细胞生长因子(肝脏疾病和细胞生长因子,黑木敏夫编辑)” Medical Review Company,136-150(1995)
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- 影响因子:0
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DAIKUHARA Yasushi其他文献
DAIKUHARA Yasushi的其他文献
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{{ truncateString('DAIKUHARA Yasushi', 18)}}的其他基金
A basic research for use of hepatocyte growth factor (HGF) for diagnosis and treatment of periodontal disease.
利用肝细胞生长因子(HGF)诊断和治疗牙周病的基础研究。
- 批准号:
12357011 - 财政年份:2000
- 资助金额:
$ 4.61万 - 项目类别:
Grant-in-Aid for Scientific Research (A)
Effect of hepatocyte growth factor/scatter factor on the development and metabolism of bone tissue : relation of regulation on fetuin gene expression.
肝细胞生长因子/分散因子对骨组织发育和代谢的影响:胎球蛋白基因表达调控的关系。
- 批准号:
10470391 - 财政年份:1998
- 资助金额:
$ 4.61万 - 项目类别:
Grant-in-Aid for Scientific Research (B).
A new diagnostic method for periodontal diseases by determining hepatocyte growth factor in gingival cervical fluid with a high sensitive ELISA.
高灵敏ELISA检测牙龈宫颈液中肝细胞生长因子的牙周病诊断新方法。
- 批准号:
08557100 - 财政年份:1996
- 资助金额:
$ 4.61万 - 项目类别:
Grant-in-Aid for Scientific Research (A)
Physiological roles of rat fetuin on bone metabolism
大鼠胎球蛋白对骨代谢的生理作用
- 批准号:
08457492 - 财政年份:1996
- 资助金额:
$ 4.61万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Studies on Relation Between Calcification of Tissues and Biosynthesis of a 59 kDa Sialoprotein from Rat Mandible, Using a Monoclinal Antibody.
使用单斜抗体研究组织钙化与大鼠下颌骨 59 kDa 唾液酸蛋白生物合成之间的关系。
- 批准号:
01480435 - 财政年份:1989
- 资助金额:
$ 4.61万 - 项目类别:
Grant-in-Aid for General Scientific Research (B)