HEAT SHOCK PROTEIN GENE EXPRESSION IN RESPONSE TO STRESS AND AGING

响应压力和衰老的热休克蛋白基因表达

• 批准号: 3802306
• 负责人: N J HOLBROOK
• 金额: --
• 依托单位: NATIONAL INSTITUTE ON AGING
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3802306
• 关键词: adrenal glands; adrenocorticotropic hormone; aging; gene expression; genetic regulation; homeostasis; hormone regulation /control mechanism; hypothalamic pituitary axis; laboratory rat; physiologic stressor; pituitary adrenal axis; stress; stress proteins; sympathetic nervous system; vascular smooth muscle

Heat shock proteins (HSPs), a group of highly conserved proteins induced in response to a variety of cellular stresses, appear to be critical for maintaining cellular homeostasis. In this project we are examining the expression of HSPs in rodents in response to physiological stresses in vivo. Our previous studies had demonstrated that simply restraining a rat would elicit the induction of HSP70, the major HSP, in the adrenal gland. More recently, we showed that major vascular structures also elicit this response. Expression of HSP70 in response to restraint is markedly reduced in aged animals. We are currently focusing on the mechanism whereby HSPs are selectively induced in the adrenal and vascular tissues with the hope of understanding why the response declines with age. We have shown that adrenal HSP70 expression with restraint is confined to the cortex of the gland and is dependent on adrenocorticotropic hormone (ACTH). Vascular HSP70 expression occurs in the smooth muscle tissue and is dependent on adrenergic stimulation. Thus, the adrenal and vascular HSP70 expression are differentially regulated. However, both appear to be linked to the classical neuroendocrine stress response which is manifested by the activation of the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system.

热休克蛋白（Heat shock proteins，HSPs）是一组在细胞内诱导表达的高度保守的蛋白质， 对各种细胞压力的反应，似乎是至关重要的， 维持细胞内环境稳定 在这个项目中，我们正在研究 啮齿动物对生理应激反应中热休克蛋白的表达 vivo. 我们之前的研究已经证明， 将引起肾上腺中主要HSP 70的诱导。 最近，我们发现主要的血管结构也会引起这种变化， 反应 应激反应中HSP 70的表达明显减少 老年动物 我们目前的重点是热休克蛋白 在肾上腺和血管组织中选择性诱导， 理解为什么反应会随着年龄的增长而下降。 我们已经证明 肾上腺HSP 70表达受限于皮质， 肾上腺素依赖于促肾上腺皮质激素（ACTH）。 血管 HSP 70表达发生在平滑肌组织中，并依赖于 肾上腺素能刺激 因此，肾上腺和血管HSP 70的表达 受到不同的调节。 然而，两者似乎都与 典型的神经内分泌应激反应，表现为 下丘脑-垂体-肾上腺轴和交感神经系统的激活 神经系统