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小鼠视交叉上核中丝裂原活化蛋白激酶磷酸化的时空调节

Spatial and temporal regulation of mitogen-activated protein kinase phosphorylation in the mouse suprachiasmatic nucleus.

作者信息

Nakaya Michio, Sanada Kamon, Fukada Yoshitaka

机构信息

Department of Biophysics and Biochemistry, Graduate School of Science, The University of Tokyo, Science Bldg. 3, Room-218A, 2-11-16 Yayoi, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.

出版信息

Biochem Biophys Res Commun. 2003 Jun 6;305(3):494-501. doi: 10.1016/s0006-291x(03)00791-5.

Abstract

Circadian and photic regulation of mitogen-activated protein kinase (MAPK) has been shown to associate closely with the function of the circadian clock in vertebrate clock tissues such as the mouse suprachiasmatic nucleus (SCN). Here we show that, in the central region of the mouse SCN, MAPK exhibited circadian and daily rhythms in phosphorylation with a peak at (subjective) night, and this activation was sustained for at least 8 h. In contrast, in the dorsomedial region of the SCN, MAPK showed an overt rhythm in phosphorylation with a transient peak at early subjective day, which was antiphase to that in the central region. Noticeably, the phospho-MAPK-immunoreactive cells observed in the dorsomedial region were distributed from the rostral to the caudal end of the SCN, whereas those observed in the central region were localized within the middle SCN along the rostral-caudal axis. Furthermore, a 15-min light pulse given at subjective night transiently evoked MAPK phosphorylation throughout the ventrolateral region of the SCN peaking within 15 min after the light onset, whereas nighttime-phosphorylated MAPK signals in the central-middle SCN become undetectable within 60 min after the light onset. Thus, the mode of circadian and photic regulation of MAPK phosphorylation varies remarkably among the three subregions within the SCN, suggesting divergent and cell type-specific roles of MAPK in the clock system of the mouse SCN.

摘要

有丝分裂原激活蛋白激酶(MAPK)的昼夜节律和光调节已被证明与脊椎动物生物钟组织(如小鼠视交叉上核(SCN))中的生物钟功能密切相关。在此我们表明,在小鼠SCN的中央区域,MAPK磷酸化呈现昼夜节律和每日节律,在(主观)夜间达到峰值,并且这种激活持续至少8小时。相比之下,在SCN的背内侧区域,MAPK磷酸化呈现明显的节律,在主观日早期出现短暂峰值,与中央区域的峰值呈反相。值得注意的是,在背内侧区域观察到的磷酸化MAPK免疫反应性细胞从SCN的头端分布到尾端,而在中央区域观察到的细胞沿头尾轴位于SCN的中部。此外,在主观夜间给予15分钟的光脉冲会在SCN的整个腹外侧区域短暂诱发MAPK磷酸化,在光照开始后15分钟内达到峰值,而在光照开始后60分钟内,中央 - 中部SCN中夜间磷酸化的MAPK信号变得不可检测。因此,MAPK磷酸化的昼夜节律和光调节模式在SCN内的三个亚区域之间存在显著差异,这表明MAPK在小鼠SCN的生物钟系统中具有不同且细胞类型特异性的作用。

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