Phosphorylation of transcription factor cyclic-AMP response element binding protein mediates c-fos induction elicited by sustained hypertension in rat nucleus tractus solitarii
Phosphorylation of transcription factor cyclic-AMP response element binding protein mediates c-fos induction elicited by sustained hypertension in rat nucleus tractus solitarii
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DOI：
10.1016/s0306-4522(98)00273-5
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发表时间：
1999-02-01
期刊：
影响因子：
3.3
通讯作者：
Chan, SHH
中科院分区：
文献类型：
--
作者：
Chan, JYH;Chen, WC;Chan, SHH
我们研究了cAMP反应元件结合蛋白信号在麻醉大鼠孤束核压力感受器激活诱导即刻早期基因c-fos中的作用。持续高血压患者的动脉压力感受器的激活显著增加了孤束核尾侧核中对检测Ser(133)磷酸化的环-AMP反应元件结合蛋白的抗血清免疫反应的神经元的数量。这意味着环-AMP反应元件结合蛋白的磷酸化增加，随后孤束核神经元中Fos蛋白的表达增加。向孤束核双侧微量注射针对cAMP反应元件结合蛋白起始点的硫代反义寡核苷酸，可明显降低磷酸化的cAMP反应元件结合蛋白对压力感受器激活的免疫反应性。伴随着c-fos信使RNA转录和Fos蛋白表达的下降，以及压力感受器反射反应的明显增强。对照注射正义寡核苷酸或人工脑脊液无效。这些结果表明，环-AMP反应元件结合蛋白的磷酸化在持续性高血压诱导的孤束核Fos表达中起关键作用。因此，环-AMP反应元件结合蛋白的磷酸化可能是孤束核Fos蛋白长期抑制压力感受性反射反应的重要早期核事件。(C)1998年IBRO。爱思唯尔科学有限公司出版。
We investigated the role of cyclic-AMP response element binding protein signaling in the induction of the immediate-early gene c-fos by baroreceptor activation in neurons of the nucleus tractus solitarii of anesthetized rats. Activation of the arterial baroreceptors with sustained hypertension significantly increased the number of neurons in the caudal nucleus tractus solitarii that were immunoreactive to an antiserum that detects Ser(133)-phosphorylated cyclic-AMP response element binding protein. This implied increase in phosphorylation of cyclic-AMP response element binding protein was subsequently followed by an elevation in the expression of Fos protein in neurons of the nucleus tractus solitarii. Microinjection bilaterally into the nucleus tractus solitarii of a phosphorothioated antisense oligonucleotide directed against the initiation site of cyclic-AMP response element binding protein messenger RNA discernibly reduced the manifested immunoreactivity of phosphorylated cyclic-AMP response element binding protein in response to baroreceptor activation. This was accompanied by a decline in the transcription of c-fos messenger RNA and the expression of Fos protein, along with an appreciable potentiation of the baroreceptor reflex response. Control injections of the sense oligonucleotide or artificial cerebrospinal fluid were ineffective.These findings suggest that phosphorylation of cyclic-AMP response element binding protein is crucial to Fos expression in the nucleus tractus solitarii elicited by sustained hypertension. As such, phosphorylation of cyclic-AMP response element binding protein may be an important early nuclear event that mediates the long-term inhibitory modulation of the baroreceptor reflex response by Fos protein at the nucleus tractus solitarii. (C) 1998 IBRO. Published by Elsevier Science Ltd.