Effect of ethanol on the regulation of corticotropin-releasing factor (CRF) gene expression
Effect of ethanol on the regulation of corticotropin-releasing factor (CRF) gene expression
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DOI：
10.1016/j.mcn.2005.04.002
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发表时间：
2005-07-01
影响因子：
3.5
通讯作者：
Rivier, C
中科院分区：
文献类型：
--
作者：
Li, ZQ;Kang, SS;Rivier, C
乙醇在体内刺激下丘脑-垂体-肾上腺轴活动。为了确定乙醇调节促肾上腺皮质激素释放因子（CRF）基因表达的细胞和分子机制，我们比较了乙醇和毛喉素对下丘脑原代细胞培养物中CRF肽分泌和信使RNA水平的影响，以及对NG 108 -15细胞系中CRF启动子活性的影响。CRF分泌，mRNA水平和基因转录显着增加响应乙醇或毛喉素。突变的cAMP反应元件（CRE）降低荧光素酶活性的基础条件下，以及在响应毛喉素或乙醇。另一方面，具有5个CRE重复序列的质粒产生显著升高的基础荧光素酶活性和显著增加的乙醇上调。包含腺苷脱氨酶降低了启动子对乙醇的响应。最后，PKA抑制剂和cAMP拮抗剂都降低乙醇诱导的CRF肽分泌，基因表达和转录。这些结果表明乙醇通过cAMP/PKA依赖性途径上调CRF表达。(c)2005爱思唯尔公司All rights reserved.
Ethanol stimulates hypothalamic-pituitary-adrenal axis activity in vivo. To determine the cellular and molecular mechanisms through which ethanol regulates corticotropin-releasing factor (CRF) gene expression, we compared the effect of ethanol and forskolin on CRF peptide secretion and messenger RNA levels in hypothalamic primary cell cultures, and on CRF promoter activity in the NG108-15 cell line. CRF secretion, mRNA levels, and gene transcription significantly increased in response to ethanol or forskolin. Mutation of the cAMP- response element (CRE) reduced luciferase activity under basal conditions as well as in response to forskolin or ethanol. On the other hand, plasmid with five CRE repeats yielded dramatically elevated basal luciferase activity and significantly increased upregulation by ethanol. Inclusion of adenosine deaminase reduced the promoter response to ethanol. Finally a PKA inhibitor and a cAMP antagonist both decreased ethanol-induced CRF peptide secretion, gene expression, and transcription. These results suggest that ethanol upregulates CRF expression through cAMP/PKA-dependent pathways. (c) 2005 Elsevier Inc. All rights reserved.