cAMP influence on transcription of thrombomodulin is dependent on de novo synthesis of a protein intermediate: evidence for cohesive regulation of myogenic proteins in vascular smooth muscle.

A E Traynor, D L Cundiff, G A Soff
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Abstract

We have previously shown that cyclic adenosine monophosphate (cAMP) increases thrombomodulin (TM) mRNA and protein in vascular smooth muscle cells (VSMCs). The mechanism of that enhancement is now further defined. A time course evaluation of this effect by Northern blot analysis showed that exposure to the cAMP analog dibutyryl-cAMP and theophylline (CT) amplified TM mRNA sixfold by 3 hours. This effect was sustained through 9 hours and began to decline by 24 hours of CT exposure. In vitro exposure of VSMCs either to CT and actinomycin D or to actinomycin D alone showed equivalent half-lives for TM mRNA. This indicates that the increase in TM mRNA with CT supplementation was not the result of enhanced mRNA stability. Nuclear run-off analysis of VSMCs grown in the presence of control or CT-supplemented medium showed that the increase in TM mRNA in VSMCs with CT exposure was transcriptional. CT exposure was associated with an eightfold increase in measured TM transcription at 90 minutes. As previously reported, cAMP induced a decrease in tropomyosin and in alpha-actin mRNA species, a change that paralleled the enhancement of TM. Thus cAMP enhances transcription of this antithrombotic species while simultaneously causing diminished expression of these myogenic mRNA species. Addition of cycloheximide prevented the cAMP-mediated increase in TM mRNA and curtailed the down-regulation of myogenic mRNA species, alpha-actin, and tropomyosin. This suggests that the cAMP-mediated down-regulation of some smooth muscle-specific mRNA, including tropomyosin mRNA and alpha-actin mRNA, like the enhancement of TM transcription, is dependent on de novo protein synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)

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cAMP对血栓调节蛋白转录的影响依赖于一种蛋白质中间体的从头合成:血管平滑肌中肌原性蛋白内聚调节的证据。
我们之前已经证明环磷酸腺苷(cAMP)增加血管平滑肌细胞(VSMCs)中的血栓调节素(TM) mRNA和蛋白。现在进一步确定了这种增强的机制。Northern blot分析表明,暴露于cAMP类似物二丁基-cAMP和茶碱(CT) 3小时后,TM mRNA扩增6倍。这种影响持续了9小时,并在24小时的CT暴露中开始下降。体外暴露于CT和放线菌素D或单独暴露于放线菌素D的VSMCs显示相同的TM mRNA半衰期。这表明补充CT增加的TM mRNA并不是mRNA稳定性增强的结果。在对照或CT补充培养基中生长的VSMCs的核径流分析显示,CT暴露后VSMCs中TM mRNA的增加是转录性的。CT暴露与90分钟时测量的TM转录增加8倍相关。正如先前报道的那样,cAMP诱导原肌球蛋白和α -肌动蛋白mRNA种类的减少,这一变化与TM的增强是平行的。因此,cAMP增强了这种抗血栓形成的mRNA的转录,同时减少了这些肌源性mRNA的表达。环己亚胺的加入阻止了camp介导的TM mRNA的增加,并抑制了肌源性mRNA种类、α -肌动蛋白和原肌球蛋白的下调。这表明camp介导的一些平滑肌特异性mRNA(包括原肌球蛋白mRNA和α -肌动蛋白mRNA)的下调,与TM转录的增强一样,依赖于从头蛋白合成。(摘要删节250字)
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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