STRESS AND CARDIOVASCULAR DISEASE

我们最近发现，压力会增加甘油二酯的水平， (DAG)和蛋白激酶C（PKC）在动物脑突触体中的作用 因为睡眠不足而压力很大 我们研究的核心是快速眼动 睡眠剥夺会引发全身性应激反应， HPA轴和POMC衍生肽，生物胺， 它们的受体、特异激酶、应激蛋白和特异基因 在心血管系统内以及 中枢神经系统（CNS）和自主神经系统（ANS）， 负责调节心血管功能。 所以我们的 本项目的工作假设是：（1）压力增加了 阿黑皮素原（POMC）衍生肽，特别是γ-2-MSH [1-39];（2）这些增加可能与增加相关 血压和心率;（3）有特定的蛋白质 在应激过程中激活的激酶以及这些激酶的激活 蛋白激酶在POMP刺激后进一步增强， 衍生肽;（4）有特定的应激蛋白， （5）有特定的POMC基因， 这些POMC基因在应激时被激活， 在相同的细胞中。 因为这是一个多方调查员， 跨学科的方法，这个项目的目标是组装一个 对压力和压力研究感兴趣的教师的临界质量 心血管疾病进行调查的细胞， 分子、化学、生理和行为机制 压力与心血管疾病 教师的参与 成员如下：（1）罗宾逊博士，作为活动领导人， 项目主任将负责整个研究计划。（二） 博士罗宾逊和科班博士将专注于确定POMC的水平- 衍生肽，特别是γ-2-MSH和ACTH[1-39]，和 睡眠剥夺应激动物血浆中的儿茶酚胺， 检查这些变化是否与 心血管参数 休斯博士将重点研究 诱导特异性蛋白激酶（aim 2）和特异性基因（aim 3） 睡眠剥夺后，POMC衍生肽是否增加 这些酶的诱导。 罗宾逊博士将协助休斯博士 免疫细胞化学和原位杂交研究涉及这些 目标。 Koban博士将专注于识别特定的应激蛋白 睡眠剥夺（目标2b-i）和Dr. Delauder将专注于应激蛋白的物理特性， 它们与A #2b-ii中多巴胺-β-羟化酶的相互作用。

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.