Blake M J, Buckley D J, Buckley A R
Department of Pharmacology and Toxicology, University of North Dakota School of Medicine, Grand Forks 58203.
Endocrinology. 1993 Mar;132(3):1063-70. doi: 10.1210/endo.132.3.8095012.
The induction of heat shock proteins (HSPs) by cellular stress and activation of the hypothalamic-pituitary-adrenal axis and sympathetic nervous system by physiological stress are biological responses that aid in the maintenance of cellular and organismal homeostasis, respectively. Based on previous studies, we have hypothesized that HSPs play a functional role in neural and endocrine stress response mechanisms in mammalian organisms. To determine the endocrine and/or neural components regulating stress-induced HSP70 expression in vivo, we have employed the long-acting synthetic propylergoline dopamine agonist CQP 201-403 (CQP). We report the novel observation that CQP mimics the effect of restraint stress to induce HSP70 expression in both adrenal gland and aorta of the rat. The presence of CQP-induced HSP70 mRNA and protein was preceded by the activation of a protein factor capable of binding to the heat shock transcriptional control element. CQP-induced HSP70 expression in the adrenal gland was restricted to the cortex, as previously observed in restraint-stressed animals. However, the distribution of expression among the three cortical layers was distinct. Hypophysectomy virtually eliminated the effects of CQP on the adrenal gland and markedly reduced HSP70 induction in the aorta. Collectively, these results provide evidence that dopaminergic systems contribute to the physiological regulation of HSP70 expression in adrenal gland and aorta directly through actions on receptors in responsive tissues and/or indirectly through the release of pituitary hormones.
细胞应激诱导热休克蛋白(HSPs)以及生理应激激活下丘脑-垂体-肾上腺轴和交感神经系统,分别是有助于维持细胞和机体稳态的生物学反应。基于先前的研究,我们推测HSPs在哺乳动物机体的神经和内分泌应激反应机制中发挥功能性作用。为了确定体内调节应激诱导的HSP70表达的内分泌和/或神经成分,我们使用了长效合成丙麦角林多巴胺激动剂CQP 201-403(CQP)。我们报告了一项新的观察结果,即CQP模拟束缚应激的作用,在大鼠的肾上腺和主动脉中诱导HSP70表达。在CQP诱导的HSP70 mRNA和蛋白出现之前,有一个能够与热休克转录控制元件结合的蛋白质因子被激活。正如在束缚应激动物中先前观察到的那样,CQP在肾上腺中诱导的HSP70表达仅限于皮质。然而,在三个皮质层中的表达分布是不同的。垂体切除几乎消除了CQP对肾上腺的影响,并显著降低了主动脉中HSP70的诱导。总的来说,这些结果提供了证据,表明多巴胺能系统直接通过作用于反应组织中的受体和/或间接通过垂体激素的释放,对肾上腺和主动脉中HSP70表达的生理调节做出贡献。