在培养的纤维细胞中生物钟的分子机制
K Yagita1, F Tamanini, G T van Der Horst
1Division of Molecular Brain Science, Department of Brain Sciences, Kobe University Graduate School of Medicine, Chuo-ku, Kobe 650-0017, Japan.
概括
哺乳动物中的周围昼夜振荡器,就像上神核 (SCN) 中的振荡器一样,具有相同的分子机制. 功能性加密染色体 (mCry) 在中央和外围组织中对这些生物节奏至关重要.
科学领域:
- 时间生物学 时间生物学
- 分子生物学分子生物学
- 哺乳动物生理学哺乳动物生理学
背景情况:
- 哺乳动物中的中央昼夜节律起器是上神核 (SCN).
- 周围组织也含有昼夜振荡器,但它们与SCN相对的分子特征尚未完全理解.
- 加密染色体 (mCry) 是已知的哺乳动物昼夜时钟的组成部分.
研究的目的:
- 为了研究培养纤维细胞中外围昼夜振荡器的分子同一性.
- 将纤维细胞振荡器与哺乳动物的SCN振荡器进行比较.
- 确定加密染色体 (mCry) 在周围昼夜节律中的作用.
主要方法:
- 利用来自mCry突变小鼠的野生类型和mCry缺陷细胞系.
- 在培养纤维细胞中分析了已知的时钟基因的时间表达特征.
- 评估mRNA节律,蛋白质定位和昼夜振荡周期长度.
主要成果:
- 外围纤维细胞振荡器表现出与SCN振荡器相同的时间表达特征.
- 关键特征如mRNA节律分相 (例如,Bmal1和mPer基因) 和蛋白质核进入延迟被保留.
- 在mCry缺乏的细胞系中没有振荡,这证实了mCry的重要作用.
- 发现mCRY蛋白可以控制这些外周节律的周期长度.
结论:
- 哺乳动物纤维细胞中的周围昼夜振荡器在分子上与SCN心脏起器完全相同.
- 功能性加密染色体 (mCry) 对于中央和外围生物钟的运行是不可或缺的.
- 这些发现突出了在不同哺乳动物组织中基础的昼夜定时的保存分子机制.
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