Effect of Diet and Hormone on the Regulation of Body Protein Synthesis

饮食和激素对体内蛋白质合成调节的影响

• 批准号: 10460056
• 负责人: NOGUCHI Tadashi
• 金额: $ 8.51万
• 依托单位: THE UNIVERSITY OF TOKYO
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B).
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-10460056/
• 关键词: Insulin-like growth factor-1; IGF-binding protein; insulin; translation initiation factor; transcription factor; protein deficiency; 肝臓核因子; 翻訳開始因子結合タンパク質

Protein metabolism is regulated by many factors including hormonal and nutritional factors. The author showed that body protein gain or loss is well explained by the plasma concentrations of insulin-like growth factors (IGFs) and their specific binding proteins called IGFBPs. Particularly, plasma concentration of IGFBP-1 increases greatly under protein deficiency or under enhanced glucocortocoid secretion or under insulin deficiency. These increases in plasma IGFBP-1 concentration is correlated to the increase in the content of IGFBP-1 mRNA in liver or the increase in the transcription rate of IGFBP-1 gene. In the present investigations, the mechanism of the increase in the IGFBP-1 gene has been analyzed.The author identified an amino acid-responsive element in the 5'upstream region of IGFBP-1 gene. Furthermore, he showed that the binding of specific transcription factors is important for the increase in the transcription rate of IGFBP-1 gene.The above results made it possible to explain the molecular mechanisms of the regulation of whole body protein metabolism as affected by dietary and hormonal factors.

蛋白质代谢受多种因素调控，包括激素和营养因素。作者表明，血浆中胰岛素样生长因子（IGFs）及其特异性结合蛋白（igfbp）的浓度可以很好地解释体内蛋白质的增加或减少。特别是在蛋白质缺乏或糖皮质激素分泌增强或胰岛素缺乏的情况下，IGFBP-1的血浆浓度显著升高。血浆IGFBP-1浓度升高与肝脏IGFBP-1 mRNA含量升高或IGFBP-1基因转录率升高有关。在目前的研究中，我们分析了IGFBP-1基因增加的机制。作者在IGFBP-1基因的上游5'区发现了一个氨基酸响应元件。此外，他还发现特异性转录因子的结合对IGFBP-1基因转录率的提高很重要。上述结果为解释受饮食和激素因素影响的全身蛋白质代谢调控的分子机制提供了可能。

项目成果

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Imae, M.、Inoue, Y.、Fu, Z.W.、Kato, H.、Noguchi, T.：“肝细胞核因子 3 三个成员的基因表达受营养和激素因素的差异调节。”J.Endocrinol

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Koide, T.：“胰岛素样生长因子-I 增强 FRTL-5 细胞中促甲状腺素诱导的蛋白质合成：蛋白质合成和 DNA 合成诱导的比较。”

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Uchijima, Y. Noguchi, T. 等人：“地塞米松稳定大鼠肝细胞原代培养物中的 IGFBP-1 mRNA。内分泌 J.. 46. 471-476 (1999)