Local receptors as novel regulators for peripheral clock expression.
Local receptors as novel regulators for peripheral clock expression.
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DOI：
10.1096/fj.13-243295
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发表时间：
2014-11
期刊：
影响因子：
--
通讯作者：
Chen Y
中科院分区：
文献类型：
--
作者：
Wu C;Sui G;Archer SN;Sassone-Corsi P;Aitken K;Bagli D;Chen Y
哺乳动物的昼夜节律控制由大脑视交叉上核（SCN）中的中央时钟和其他组织中的同步外周时钟决定。越来越多的证据表明，外周时钟也存在独立于 SCN 的调节。我们研究了兴奋性受体的激活如何影响收缩器官（膀胱）中的时钟蛋白 PERIOD 2 (PER2)。 PERIOD2::荧光素酶敲入小鼠用于报告膀胱组织中的实时 PER2 昼夜节律动态。膀胱壁有节律性 PER2 活动，周期约为 24 小时，峰值出现于 12 小时。激动剂对毒蕈碱和嘌呤能受体的激活将峰值移至较早的时间（分别为7.2±2.0和7.2±0.9小时）。 PER2 表达对机械刺激也敏感。衰老显着抑制 PER2 表达及其对激动剂的反应。最后，毒蕈碱激动剂诱导的平滑肌收缩也表现出昼夜节律。这些数据确定了新的调节因子，即内源性受体，除了介导中央控制外，还可以确定本地时钟活动。此外，本地时钟似乎使受体活动与肌肉收缩的昼夜节律相互协调。受体和外周时钟之间的相互作用代表了维持生理功能的重要机制，其失调可能导致与年龄相关的器官疾病。-Wu, C., Sui, G., Archer, S. N., Sassone-Corsi, P., Aitken, K., Bagli, D., Chen, Y. 局部受体作为外周时钟表达的新型调节剂。
Mammalian circadian control is determined by a central clock in the brain suprachiasmatic nucleus (SCN) and synchronized peripheral clocks in other tissues. Increasing evidence suggests that SCN-independent regulation of peripheral clocks also occurs. We examined how activation of excitatory receptors influences the clock protein PERIOD 2 (PER2) in a contractile organ, the urinary bladder. PERIOD2::LUCIFERASE-knock-in mice were used to report real-time PER2 circadian dynamics in the bladder tissue. Rhythmic PER2 activities occurred in the bladder wall with a cycle of ∼24 h and peak at ∼12 h. Activation of the muscarinic and purinergic receptors by agonists shifted the peak to an earlier time (7.2±2.0 and 7.2±0.9 h, respectively). PER2 expression was also sensitive to mechanical stimulation. Aging significantly dampened PER2 expression and its response to the agonists. Finally, muscarinic agonist-induced smooth muscle contraction also exhibited circadian rhythm. These data identified novel regulators, endogenous receptors, in determining local clock activity, in addition to mediating the central control. Furthermore, the local clock appears to reciprocally align receptor activity to circadian rhythm for muscle contraction. The interaction between receptors and peripheral clock represents an important mechanism for maintaining physiological functions and its dysregulation may contribute to age-related organ disorders.—Wu, C., Sui, G., Archer, S. N., Sassone-Corsi, P., Aitken, K., Bagli, D., Chen, Y. Local receptors as novel regulators for peripheral clock expression.
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影响因子：
25
作者：
Masri, Selma;Sassone-Corsi, Paolo
通讯作者：
Sassone-Corsi, Paolo
影响因子：
4.5
作者：
Christensen BC;Houseman EA;Marsit CJ;Zheng S;Wrensch MR;Wiemels JL;Nelson HH;Karagas MR;Padbury JF;Bueno R;Sugarbaker DJ;Yeh RF;Wiencke JK;Kelsey KT
通讯作者：
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影响因子：
9.2
作者：
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通讯作者：
Kyriacou, CP
DOI：
10.1097/mco.0b013e32834ad94b
发表时间：
2011-11-01
影响因子：
3.1
作者：
Gimble, Jeffrey M.;Sutton, Gregory M.;Bunnell, Bruce A.
通讯作者：
Bunnell, Bruce A.
影响因子：
20.1
作者：
Illi, B;Scopece, A;Gaetano, C
通讯作者：
Gaetano, C