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MOLECULAR MECHANISM OF ADRENERGIC PLASTICITY

肾上腺素能可塑性的分子机制

基本信息

批准号：
3413879
负责人：
GALE Louise CRAVISO
金额：
$ 13.68万
依托单位：
UNIVERSITY OF NEVADA RENO
依托单位国家：
美国
项目类别：
财政年份：
1989
资助国家：
美国
起止时间：
1989-09-01 至 1992-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3413879
关键词：
RNA biosynthesis chromaffin cells enzyme mechanism gene expression genetic regulation genetic translation messenger RNA muscarinic receptor neural plasticity nicotinic receptors nucleic acid sequence posttranslational modifications protein biosynthesis secretion stimulant /agonist tissue /cell culture tyrosine

项目摘要

One of the basic principles important to the function of excitable neurosecretory cells is that the strength of synaptic activity modulates the secretory capacity of the cells. One of the best examples of this kind of biochemical neuroplasticity is the modulation of catecholamine synthesis which occurs in response to increased afferent neural activity in the peripheral and central nervous systems. In the peripheral nervous system, for example, both the short- and long-term activity of the rate-limiting enzyme in the catecholamine synthetic pathway, tyrosine hydroxylase, is modulated by cholinergic activity. In our previous studies, we focused on the short-term regulation of this enzyme using a convenient model system, isolated bovine adrenal chromaffin cells. Recently we have established that not only is short-term cholinergic regulation expressed in these cells, but also that the levels of tyrosine hydroxylase mRNA, and protein are modulated in response to cholinergic receptor occupancy. In the research presented in this application, we will utilize this in vitro induction of tyrosine hydroxylase levels by cholinergic agonists to understand and characterize the molecular mechanisms controlling the increased level of tyrosine hydroxylase mRNA and protein. We will determine the role of cholinergic receptor occupancy in regulating the level of tyrosine hydroxylase mRNA synthesis and the translation of this message into tyrosine hydroxylase enzyme protein. We will establish the basis for the temporal disparity between the time course of the increase in message level and the increase in tyrosine hydroxylase enzyme activity. Lastly, we will evaluate the role of ribonucleotide sequences within the untranslated region of tyrosine, hydroxylase mRNA in influencing the translation efficiency of the tyrosine hydroxylase message.

对兴奋性的作用很重要的基本原则之一神经分泌细胞是突触活动的强度调节细胞的分泌能力。最好的例子之一就是一种生化神经可塑性是儿茶酚胺的调制由于传入神经活动增加而发生的合成在外周和中枢神经系统中。在周围神经紧张中系统，例如，短期和长期的活动，儿茶酚胺合成途径中的限速酶酪氨酸羟基酶，受胆碱能活动的调节。在我们之前的研究中，我们重点研究了这种酶的短期调节。方便的模型体系，分离牛肾上腺嗜铬细胞。最近我们发现，不仅短期胆碱能在这些细胞中表达的调控，也是酪氨酸羟基酶mRNA和蛋白被调节以响应胆碱能受体占有率。在本应用程序中提供的研究中，我们将在胆碱能激动剂体外诱导酪氨酸羟化酶水平了解和表征控制细胞生长的分子机制酪氨酸羟基酶基因和蛋白水平升高。我们会确定胆碱能受体占位在调节酪氨酸羟基酶mRNA的合成水平及其翻译信息转化为酪氨酸羟基酶蛋白。我们将建立时间差距的基础是时间进程之间的增加在消息水平和酪氨酸羟基酶的增加活动。最后，我们将评估核糖核苷酸序列的作用在酪氨酸的非翻译区，羟基酶mRNA在影响酪氨酸羟化酶翻译效率的因素留言。