STRESS AND CARDIOVASCULAR DISEASE

压力与心血管疾病

• 批准号: 6348231
• 负责人: T. Joan Robinson
• 金额: $ 28.04万
• 依托单位: MORGAN STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-30 至 2002-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6348231
• 关键词: adrenocorticotropic hormone; blood pressure; cardiovascular disorder; cardiovascular function; catecholamines; enzyme activity; enzyme induction /repression; health science research potential; heart rate; immunocytochemistry; in situ hybridization; isozymes; laboratory rat; melanocyte stimulating hormone; minority institution research support; mitogen activated protein kinase; northern blottings; physiologic stressor; proopiomelanocortin; protein kinase C; protein tyrosine kinase; sleep deprivation; stress; western blottings

We recently showed that stress increases the levels of diacylglycerol (DAG) and Protein Kinase C (PKC) in synaptosomes from the brain of animals stressed by sleep deprivation. The centerpiece of our study is that REM sleep deprivation elicits a generalized systemic stress response involving the HPA axis and the activation of POMC-derived peptides, biogenic amines, their receptors, specific kinases, stress proteins and specific genes within the cardiovascular system as well as selected regions of the central nervous system (CNS) and the autonomic nervous system (ANS) that are responsible for regulating cardiovascular function. Therefore, our working hypotheses in this project are: (1) stress increases the levels of proopiomelanocortin (POMC)-derived peptides, in particular, gamma-2-MSH and ACTH[1-39]; (2) that these increases can be correlated with increases in blood pressure and heart rate; (3) that there are specific proteins kinases that are activated during stress and the activation of these protein kinases are further enhanced following stimulation with POMP- derived peptides; (4) there are specific stress proteins that are induced in response to stress; and (5) there are specific POMC genes that are activated in response to stress and these POMC genes are colocalized within the same cells. Since this is a multi-investigator, interdisciplinary approach, the goal of this project is to assemble a critical mass of faculty with research interest in Stress and Cardiovascular Diseases to conduct investigations into the cellular, molecular, chemical, physiological and behavioral mechanisms underlying Stress and Cardiovascular Diseases. The involvement of the faculty members will be as follows: (1) Dr. Robinson, as activity leader and Program Director will be responsible for the overall research program. (2) Dr. Robinson and Dr. Koban will focus on determining the levels of POMC- derived peptides, in particular gamma-2-MSH and ACTH[1-39] and catecholamines in the plasma of animals stressed by sleep deprivation and examine whether these changes are correlated with changes in cardiovascular parameters. Dr. Hughes will focus on identifying whether specific protein kinases (aim 2) and specific genes (aim 3) are induced following sleep deprivation and whether POMC-derived peptides increases the induction of these enzymes. Dr. Robinson will assist Dr. Hughes in the immunocytochemical and in situ hybridization studies involved in these aims. Dr. Koban will focus on identifying the specific stress proteins that are induced during stress by sleep deprivation (aim 2b-i) and Dr. Delauder will focus on the physical properties of stress proteins and their interactions with dopamine-beta-hydroxylase in A #2b-ii.

我们最近表明，应力增加了二酰基甘油的水平 （DAG）和蛋白激酶C（PKC）来自动物大脑的突触体中的（PKC） 由于睡眠不足而压力。 我们研究的核心是REM 睡眠剥夺引起广泛的全身压力反应，涉及 HPA轴和POMC衍生肽的激活，生物胺， 它们的受体，特定激酶，应激蛋白和特定基因 在心血管系统中以及选定的区域 中枢神经系统（CNS）和自主神经系统（ANS） 负责调节心血管功能。 因此，我们的 该项目中的工作假设是：（1）压力增加了 proOpiomelanocortin（POMC）衍生的肽，尤其是γ-2-MSH 和ACTH [1-39]； （2）这些增加可以与增加 血压和心率； （3）有特定的蛋白质 在压力期间激活的激酶和激活 通过蓬松刺激后，蛋白激酶进一步增强 衍生的肽； （4）有特定的应力蛋白是被诱导的 响应压力； （5）有特定的POMC基因是 因应力而激活，这些POMC基因共定位 在同一单元格中。 由于这是一个多入侵者，所以 跨学科的方法，该项目的目标是组装 对压力和研究兴趣的教师的关键群众 心血管疾病以对细胞进行调查， 分子，化学，生理和行为机制 压力和心血管疾病。 教师的参与 成员将如下：（1）Robinson博士，作为活动负责人和 计划主管将负责整个研究计划。 （2） 鲁滨逊博士和科班博士将专注于确定pomc的水平 衍生的肽，尤其是γ-2-MSH和ACTH [1-39]和 在睡眠不足和 检查这些变化是否与变化相关 心血管参数。 休斯博士将专注于确定是否 特定的蛋白激酶（AIM 2）和特定基因（AIM 3）被诱导 在睡眠剥夺之后以及POMC衍生的肽是否增加 这些酶的诱导。 鲁滨逊博士将协助休斯博士 这些涉及的免疫细胞化学和原位杂交研究 目标。 Koban博士将专注于识别特定的应力蛋白 通过睡眠剥夺（AIM 2B-I）和Dr. Delauder将专注于应力蛋白的物理特性和 它们与＃2b-II中多巴胺β-羟化酶的相互作用。