STRESS INDUCED CHANGES IN GENE EXPRESSION

压力引起的基因表达变化

• 批准号: 2037703
• 负责人: Esther Louise Sabban
• 金额: $ 21.12万
• 依托单位: NEW YORK MEDICAL COLLEGE
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-12-01 至 1998-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2037703
• 关键词: DNA footprinting; adrenal medulla; angiotensin II; aromatic L aminoacid decarboxylase; catecholamines; denervation; dopamine beta monooxygenase; enzyme induction /repression; gel mobility shift assay; gene expression; glucocorticoids; hypophysectomy; immobilization of body part; laboratory rat; methyltransferase; neuroendocrine system; neuropeptides; nitric oxide; pituitary adrenal axis; splanchnic nerves; stress; stressor; sympathetic ganglion; transcription factor; tyrosine 3 monooxygenase

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.

压力在心血管疾病的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）、胃肠道疾病（胃溃疡）以及 在免疫疾病和癌症的发展中发挥着许可作用。 据估计，除了人类的痛苦之外，与压力有关的疾病还导致 每年花费约 3000 亿美元，占总成本的近三分之二 在医生办公室看到的疾病。 交感肾上腺系统是其中之一 第一个系统在压力期间激活。 尽管在这方面做了很多工作 关于应激的生理学，人们对应激的分子变化知之甚少。 应激中的基因表达。 我们最近的研究表明，有 肾上腺儿茶酚胺基因表达发生巨大变化 固定间隔相对较短的生物合成酶 压力。 长期目标是确定基因如何受到调控 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压力调节。 具体来说： 1. 检验神经元和体液因子激活的假设 在压力期间影响肾上腺髓质的过度表达 儿茶酚胺生物合成途径响应应激。 2. 检验压力引起基因变化的假设 表达涉及基因的转录激活 儿茶酚胺生物合成酶受多种交易因子影响。 3. 检验单次和重复固定应力的假设 引起儿茶酚胺生物合成酶的基因表达增加 交感神经节是循环的主要贡献者 去甲肾上腺素。 更好地了解压力机制，应该很有帮助 最终设计出药物来保护个人免受此类影响 损害，特别是当预期暴露于慢性或反复的损害时 压力。 它还将使人们更好地了解危险 不同程度的压力以及如何减轻这些危险。