Non-enzymatic glycosylation of proteins in biological sytem and its physiological significance in aging process.

生物系统中蛋白质的非酶糖基化及其在衰老过程中的生理意义。

基本信息

  • 批准号:
    62570136
  • 负责人:
  • 金额:
    $ 1.47万
  • 依托单位:
  • 依托单位国家:
    日本
  • 项目类别:
    Grant-in-Aid for General Scientific Research (C)
  • 财政年份:
    1987
  • 资助国家:
    日本
  • 起止时间:
    1987 至 1988
  • 项目状态:
    已结题

项目摘要

Nonenzymatic glycosylation of proteins with glucose named the Maillard reaction leads, through a Schiff base adduct and Amadori rearrangement products, to advanced glycosylation end product (AGE) with fluorescence, brown color and cross-linked property. Protein modification in vivo by the Maillard reaction. Particularly age-products, is believed to play an important role in deabetic complications or aging processes, although nothing is known about a chemical structure(s) of AGE-proteins. In the present project, we elucidated the biological property of AGE-products. An attempt was also made to determine the chemical structure of AGE-product(s). Following results were obtained.1. AGE-proteins such as AGE-albumin and AGE-hemoglobin underwent receptor-mediated endocytosis by macrophages or macrophage-derived cells, including rat sinusoidal liver cells, rat and murine peritoneal macrophages and human monocyte macrophages. The receptor was found to be identical to a scavenger receptor for aldehyde-modified proteins which had been discovered by us in 1986.2. Cerami et al. claimed that 2-(2-furoyl)-4(5)-(furanyl)-1H-imidazole (FFI) was involved in the recepter recognition. However, our experiment using synthesized FFI derivatives clearly showed that this was not the case.3. Determination by the radioimmunoassay using an anti-FFI antibody and by high performance liquid chromatography demonstrated that FFI was in fact an artifact generated after acid hydrolysis of AGE-proteins and subsequent reaction with ammonia, evidence against in vivo presence of FFI.4. The major fluorescent compound was isolated from AGE-l-lysine derivatives. Immunological analyses indicated that this fluorescent compound did occur to age-proteins. Its precise chemical structure is being determined.The above results taken together suggest that a structure in common among AGE-proteins might be crucial to the biological recognition by the scavenger receptor.
蛋白质与葡萄糖的非酶糖基化反应称为美拉德反应,通过席夫碱加合物和Amadori重排产物,导致具有荧光、棕色和交联性质的高级糖基化终产物(AGE)。通过美拉德反应进行的体内蛋白质修饰。特别是年龄产物,被认为在痴呆并发症或衰老过程中起重要作用,尽管对AGE蛋白的化学结构一无所知。本课题主要研究AGE产物的生物学特性。还试图确定AGE产物的化学结构。主要研究结果如下:1. AGE-蛋白如AGE-白蛋白和AGE-血红蛋白经历受体介导的巨噬细胞或巨噬细胞衍生的细胞的内吞作用,包括大鼠肝窦细胞、大鼠和小鼠腹腔巨噬细胞和人单核细胞巨噬细胞。发现该受体与我们在1986年发现的一种针对β-环糊精修饰的蛋白质的清道夫受体相同。Cerami等声称2-(2-呋喃甲酰基)-4(5)-(呋喃基)-1H-咪唑(FFI)参与受体识别。然而,我们使用合成的FFI衍生物的实验清楚地表明,情况并非如此。通过使用抗FFI抗体的放射免疫测定和通过高效液相色谱法的测定证明,FFI实际上是AGE-蛋白质的酸水解和随后与氨反应后产生的伪像,这是FFI在体内存在的证据。主要的荧光化合物是从AGE-1-赖氨酸衍生物中分离出来的。免疫学分析表明,这种荧光化合物确实发生在年龄蛋白上。以上结果表明,AGE蛋白的一个共同结构可能是清道夫受体生物识别的关键。

项目成果

期刊论文数量(21)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Horiuchi,Seikoh: Journal of Molecular Recognition. (1989)
Horiuchi,Seikoh:分子识别杂志。
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
  • 作者:
  • 通讯作者:
Horiuchi, Seikoh: "Regional ligand domain is involved in scavenger receptor-mediated recognition of maleyl-albumin by rat sinusoidal liver cells" Journal of Molecular Recognition. (1989)
Horiuchi, Seikoh:“区域配体结构域参与清道夫受体介导的大鼠肝窦肝细胞对马来酰白蛋白的识别”《分子识别杂志》。
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
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  • 通讯作者:
Horiuchi,Seikoh.: Journal of Biological Chemistry. 263. 18821-18826 (1988)
Horiuchi,Seikoh。:生物化学杂志。
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
  • 作者:
  • 通讯作者:
Murakami, Masaji: Journal of Biochemistry. 101. 729-741 (1987)
村上正二:《生物化学杂志》。
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
  • 作者:
  • 通讯作者:
Takata,Kyoko: Journal of Biological Chemistry. 263. 14819-14825 (1988)
高田恭子:生物化学杂志。
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
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HORIUCHI Seikoh其他文献

HORIUCHI Seikoh的其他文献

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{{ truncateString('HORIUCHI Seikoh', 18)}}的其他基金

Roles of CD36 and SR-BI as novel AGE-receptors
CD36 和 SR-BI 作为新型 AGE 受体的作用
  • 批准号:
    13470228
  • 财政年份:
    2001
  • 资助金额:
    $ 1.47万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
AGE Structures and their Biomedical Significance
AGE 结构及其生物医学意义
  • 批准号:
    10044305
  • 财政年份:
    1999
  • 资助金额:
    $ 1.47万
  • 项目类别:
    Grant-in-Aid for Scientific Research (A).
Role of AGE Receptors in Diabetic Complications
AGE 受体在糖尿病并发症中的作用
  • 批准号:
    11557081
  • 财政年份:
    1999
  • 资助金额:
    $ 1.47万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B).
Biological clearance system for advanced glycation end products (AGE) -Insulin signal regulates endocytic uptake of AGE-proteins
晚期糖基化终末产物 (AGE) 的生物清除系统 - 胰岛素信号调节 AGE 蛋白的内吞摄取
  • 批准号:
    09470225
  • 财政年份:
    1997
  • 资助金额:
    $ 1.47万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Molecular Biology of Acyl-coenzyme A : cholesterol Acyltransferase
酰基辅酶 A 的分子生物学:胆固醇酰基转移酶
  • 批准号:
    08044304
  • 财政年份:
    1996
  • 资助金额:
    $ 1.47万
  • 项目类别:
    Grant-in-Aid for international Scientific Research
Detemination of The Main Advanced Glycation End Product of The Maillard Reaction and Its Significance as A Biochemical Marker for Diabetic Complications
美拉德反应主要高级糖基化终产物的测定及其作为糖尿病并发症生化标志物的意义
  • 批准号:
    07557076
  • 财政年份:
    1995
  • 资助金额:
    $ 1.47万
  • 项目类别:
    Grant-in-Aid for Scientific Research (A)
Structure and Function of Receptors for Advanced Glycation End Products of the Maillard Reaction
美拉德反应高级糖基化终产物受体的结构和功能
  • 批准号:
    06454170
  • 财政年份:
    1994
  • 资助金额:
    $ 1.47万
  • 项目类别:
    Grant-in-Aid for General Scientific Research (B)

相似海外基金

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美拉德反应产生的气味物质对吸入老化的影响
  • 批准号:
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Mechanism - guided strategies for the control of the Maillard reaction
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Characterizing the impact of sugar-type and metal ion content on the Maillard reaction in low-temperature, acidic conditions
表征低温、酸性条件下糖类型和金属离子含量对美拉德反应的影响
  • 批准号:
    568808-2022
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    2022
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Development of novel techniques for production, aging and utilization of meat by the combination of proteolysis and the Maillard reaction
结合蛋白水解和美拉德反应开发肉类生产、熟化和利用的新技术
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识别美拉德反应产物的假定生物活性氧化还原特性
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