Li Ning, Cai Yanning, Zuo Xiaohong, Xu Shengli, Zhang Yanli, Chan Piu, Zhang Yu Alex
Cell Therapy Center, Xuanwu Hospital of Capital Medical University, Key Laboratory for Neurodegenerative Diseases of Ministry of Education, 45 Changchun Street, Beijing, PR China.
Biochem Biophys Res Commun. 2008 Dec 26;377(4):1179-84. doi: 10.1016/j.bbrc.2008.10.111. Epub 2008 Oct 31.
The mammalian circadian pacemaker has been localized to the hypothalamic suprachiasmatic nucleus (SCN), where a set of clock genes and their resulting proteins form interlocking transcriptional/translational feedback loops to sustain molecular and functional oscillations. Interestingly, peripheral tissues and stimulated fibroblasts have also displayed daily oscillations, which are thought to be synchronized by the SCN in vivo. However, intercellular communications between the SCN and other tissues or cells remain poorly understood. Therefore, a novel co-culture model was established in the present study to understand the interactions between central and peripheral oscillators in co-cultures of SCN slices and NIH/3T3 cells in a serum-free condition. Expression profiles of Per1 and Rev-Erb alpha were measured in NIH/3T3 cells using real-time PCR. Results demonstrated that diffusible signals released from SCN slices could regulate molecular rhythms in cultured fibroblasts. Moreover, Rev-Erb alpha oscillation was more robust and appeared earlier than Per1.
哺乳动物的昼夜节律起搏器定位于下丘脑视交叉上核(SCN),在那里一组时钟基因及其产生的蛋白质形成相互连锁的转录/翻译反馈环,以维持分子和功能振荡。有趣的是,外周组织和受刺激的成纤维细胞也表现出每日振荡,这被认为在体内由SCN同步。然而,SCN与其他组织或细胞之间的细胞间通讯仍知之甚少。因此,本研究建立了一种新型共培养模型,以了解在无血清条件下SCN切片与NIH/3T3细胞共培养时中央和外周振荡器之间的相互作用。使用实时PCR测量NIH/3T3细胞中Per1和Rev-Erbα的表达谱。结果表明,SCN切片释放的可扩散信号可调节培养的成纤维细胞中的分子节律。此外,Rev-Erbα振荡更强健且比Per1出现得更早。