BLOCK OF C-FOS AND JUNB EXPRESSION BY ANTISENSE OLIGONUCLEOTIDES INHIBITS LIGHT-INDUCED PHASE-SHIFTS OF THE MAMMALIAN CIRCADIAN CLOCK
BLOCK OF C-FOS AND JUNB EXPRESSION BY ANTISENSE OLIGONUCLEOTIDES INHIBITS LIGHT-INDUCED PHASE-SHIFTS OF THE MAMMALIAN CIRCADIAN CLOCK
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DOI：
10.1111/j.1460-9568.1995.tb00334.x
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发表时间：
1995-03-01
影响因子：
3.4
通讯作者：
HERDEGEN, T
中科院分区：
文献类型：
--
作者：
WOLLNIK, F;BRYSCH, W;HERDEGEN, T
光诱导的昼夜节律运动活动的相移与c-Jun，JunB，c-Fos和FosB转录因子在大鼠视交叉上核的表达，如本研究所示。为了探讨的重要性，c-Fos和JunB，主要表达的AP-1蛋白的相移光的影响，我们阻止c-Fos和JunB的表达在视交叉上核的雄性大鼠，在恒定的黑暗下，通过脑室内应用2 μ l的1 mM的反义硫代磷酸寡脱氧核苷酸（阿索）特异性地针对c-fos和JunB mRNA。在昼夜节律时间15的光脉冲（300勒克斯持续1小时）诱导昼夜运动活动节律的显著相移（125 +/-15分钟），而在光脉冲之前6小时应用阿索完全阻止了这种相移。应用对照无义寡脱氧核苷酸没有影响。阿索可显著降低光诱导的c-Fos和JunB蛋白的表达。与此相反，光脉冲与或不控制无义寡脱氧核苷酸诱发强烈的核c-Fos和JunB免疫反应在大鼠视交叉上核。这些结果首次表明，诱导型转录因子，如c-Fos和JunB是在成年哺乳动物神经系统的基本生物过程的重要组成部分，例如光诱导的昼夜节律起搏器的相移。
Light-induced phase shifts of circadian rhythmic locomotor activity are associated with the expression of c-Jun, JunB, c-Fos and FosB transcription factors in the rat suprachiasmatic nucleus, as shown in the present study. In order to explore the importance of c-Fos and JunB, the predominantly expressed AP-1 proteins for the phase-shifting effects of light, we blocked the expression of c-Fos and JunB in the suprachiasmatic nucleus of male rats, housed under constant darkness, by intracerebroventricular application of 2 mu l of 1 mM antisense phosphorothioate oligodeoxynucleotides (ASO) specifically directed against c-fos and junB mRNA. A light pulse (300 lux for 1 h) at circadian time 15 induced a significant phase shift (by 125 +/- 15 min) of the circadian locomotor activity rhythm, whereas application of ASO 6 h before the light pulse completely prevented this phase shift. Application of control nonsense oligodeoxynucleotides had no effect. ASO strongly reduced the light-induced expression of c-Fos and JunB proteins. In contrast, light pulses with or without the control nonsense oligodeoxynucleotides evoked strong nuclear c-Fos and JunB immunoreactivity in the rat suprachiasmatic nucleus. These results demonstrate for the first time that inducible transcription factors such as c-Fos and JunB are an essential part of fundamental biological processes in the adult mammalian nervous system, e.g. of light-induced phase shifts of the circadian pacemaker.