STRESS INDUCED CHANGES IN GENE EXPRESSION

应激在心血管疾病的发生发展中起重要作用 疾病（高血压，心脏病发作），精神疾病（抑郁症， 精神分裂症）、胃肠道疾病（胃溃疡）以及 在免疫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， 每年耗资约3000亿美元，占全球近三分之二的 在医生的办公室里看到的疾病。 交感肾上腺系统是 在压力下最先激活的系统 尽管在这方面做了大量工作， 关于应激的分子变化， 胁迫下的基因表达 我们最近的研究表明， 肾上腺儿茶酚胺基因表达的巨大变化 固定化间隔相对较短的生物合成酶 应力 长期目标是确定基因是如何被调控的， 压力，以找到预防或治疗措施。 中央 本提案中要检验的假设是， 儿茶酚胺生物合成酶受应激调节。 具体而言： 1. 检验神经和体液因素激活 在应激过程中影响肾上腺髓质的过度表达 儿茶酚胺生物合成途径响应压力。 2. 测试压力引起基因改变的假设 表达涉及基因的转录激活， 儿茶酚胺生物合成酶的几个transacting因素。 3.检验一次和多次固定压力 增强了儿茶酚胺生物合成酶的基因表达 在交感神经节，循环的主要贡献者， 去甲肾上腺素 更好地理解应激的机制，应该是很有帮助的 在最终设计药物，以保护个人免受这种 损害，特别是当预期暴露于慢性或反复 应力 它也将导致更好地了解的危险， 不同程度的压力以及如何减轻这些危险。

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.