STRESS INDUCED CHANGES IN GENE EXPRESSION

应激在心血管疾病的发生发展中起着重要作用 疾病(高血压、心脏病)、精神疾病(抑郁症、 精神分裂症)，胃肠疾病(胃溃疡)，还有 在免疫性疾病和癌症的发展中起着允许的作用。 据估计，除了人类的痛苦之外，与压力相关的疾病还会 每年耗资约3,000亿美元，占全球 在医生办公室里看到的疾病。交感-肾上腺系统是 第一批系统在压力下被激活。尽管在这方面做了很多工作 关于应激的生理学，人们对其分子变化知之甚少。 应激状态下的基因表达。我们最近的研究表明，有 肾上腺儿茶酚胺基因表达的大变化 固定化间隔较短的生物合成酶 压力。 长期目标是确定基因是如何在 压力，以便找到预防或治疗措施。中环 在这项提议中要检验的假设是 儿茶酚胺生物合成酶受到应激的调节。具体地说，就是： 1.检验神经元和体液因子被激活的假设 应激影响下肾上腺髓质的过度表达 儿茶酚胺在应激反应中的生物合成途径。 2.检验压力引起基因改变的假设 表达涉及到基因的转录激活 儿茶酚胺生物合成酶的几种作用因素。 3.检验单次和重复制动应激的假设 诱导儿茶酚胺生物合成酶基因表达增加 在交感神经节中，循环的主要贡献者 去甲肾上腺素。 更好地了解应激的机制，应该是非常有帮助的 在最终设计药物来保护个人免受这种 损害，尤其是当预计将长期或反复暴露于 压力。它还将使人们更好地理解 不同程度的压力以及如何缓解这些危险。

Stress play a significant role in the development of cardiovascular diseases (hypertension, heart attack), mental diseases (depression, schizophrenia), gastrointestinal disorders (stomach ulcers) and also plays a permissive role in development of immune diseases and in cancer. Stress related disorders are estimated, besides the human suffering, to cost roughly $300 billion annually and comprise nearly two-thirds of the ailments seen in doctors' offices. The sympathoadrenal system is one of the first systems activated during stress. Despite much work on the physiology of stress little is known regarding the molecular changes in gene expression in stress. Our recent studies indicate that there are large changes in gene expression for the adrenal catecholamine biosynthetic enzymes with relatively short intervals of immobilization stress. The long term objective is to determine how genes are regulated under stress in order to find preventive or curative measures. The central hypothesis to be tested in this proposal is that the expression of catecholamine biosynthetic enzymes is modulated by stress. Specifically: 1. Test the hypothesis that neuronal and humoral factors activated during stress influence the over expression of the adrenomedullary catecholamine biosynthetic pathway in response to stress. 2. Test the hypothesis that the stress-elicited changes in gene expression involve transcription activation of genes for the catecholamine biosynthetic enzymes by several transacting factors. 3. Test the hypothesis that a single and repeated immobilization stress elicits increased gene expression of catecholamine biosynthesis enzymes in the sympathetic ganglia, the major contributor to circulating norepinephrine. A better understanding of the mechanism of stress, should be very helpful in ultimately designing medications to protect the individual from such damage, particularly when expected to be exposed to chronic or repeated stress. It will also lead to a better understanding of the dangers of various degrees of stress and how to alleviate these dangers.