Nankova B, Devlin D, Kvetnanský R, Kopin I J, Sabban E L
Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla 10595.
J Neurochem. 1993 Aug;61(2):776-9. doi: 10.1111/j.1471-4159.1993.tb02188.x.
Repeated immobilization stress elicits a large elevation in adrenal dopamine beta-hydroxylase (DBH) mRNA levels. This study attempts to analyze the molecular mechanism of increased DBH gene expression in stress. Adrenomedullary nuclear proteins were prepared from controls and rats exposed to various intervals of immobilization stress. Electrophoretic mobility shift assays showed that repeated stress led to increased binding of adrenomedullary nuclear factors to a cis-acting regulatory element in the rat DBH promoter (DBH-1). One of the partners in the DNA-protein complex is c-Fos or a Fos-related protein. There was a correlation between promoter binding activity and elevated steady-state levels of DBH mRNA. Our data indicate that this cis regulatory element in the rat DBH promoter is functional in vivo, and increased binding of AP1-like transcription factors to this motif is induced by immobilization stress.
反复的固定应激会导致肾上腺多巴胺β-羟化酶(DBH)mRNA水平大幅升高。本研究旨在分析应激状态下DBH基因表达增加的分子机制。从对照组和暴露于不同时长固定应激的大鼠中制备肾上腺髓质核蛋白。电泳迁移率变动分析表明,反复应激导致肾上腺髓质核因子与大鼠DBH启动子(DBH-1)中的顺式作用调节元件的结合增加。DNA-蛋白质复合物中的一个结合蛋白是c-Fos或Fos相关蛋白。启动子结合活性与DBH mRNA稳态水平升高之间存在相关性。我们的数据表明,大鼠DBH启动子中的这种顺式调节元件在体内具有功能,固定应激可诱导AP1样转录因子与该基序的结合增加。