Kolbeck-Rühmkorff C, Horban A, Zimmer H G
Department of Physiology, University of Munich, Germany.
Cardiovasc Res. 1993 Nov;27(11):1998-2004. doi: 10.1093/cvr/27.11.1998.
The aim was to study the effect of pressure and volume overload on the expression of the proto-oncogenes, c-fos and c-myc, in isolated perfused working rat hearts and to compare these results with the known effects of noradrenaline.
Working rat hearts were obtained by converting the Langendorff preparation into the working mode by perfusion through the left atrium. Using specific cDNA clones, the mRNAs of c-fos and c-myc were measured by northern blots and quantified with densitometry. Total RNA was isolated from hearts after stimulation with noradrenaline (3 x 10(-8) M), after increasing afterload from 80 to 100 cm H2O, and left atrial filling pressure (preload) from 8 to 16 cm H2O for 15, 30, 60, 90, and 120 min, respectively.
The mRNAs of c-fos and c-myc were not detectable in freshly excised rat hearts. When the hearts were perfused in the working mode for 15, 30, 60, 90, and 120 min, c-fos and c-myc mRNAs were measurable, and these mRNA levels served as control baseline values that were set at 100%. When noradrenaline was infused, c-fos mRNA was increased fivefold after 30, threefold after 60, and 3.8-fold after 90 min. The mRNA of c-myc was increased 1.8-fold after 60 min and 3.8-fold after 90 min. The increase in afterload induced a threefold increase of c-fos mRNA after 30 min and a threefold increase of c-myc mRNA after 90 min. When preload was increased, c-fos mRNA rose 1.8-fold after 30 min, and c-myc mRNA twofold after 60 min and 2.8-fold after 90 min compared to the controls.
Pressure and volume overload have effects on the expression of c-fos and c-myc mRNA that are similar to those obtained with noradrenaline stimulation which induced the most pronounced signals. Our time course studies showed that c-fos mRNA always rose before c-myc mRNA. This common sequential induction pattern may have important signal function in the processes that trigger the development of cardiac hypertrophy.
研究压力和容量超负荷对离体灌注的工作大鼠心脏中原癌基因c-fos和c-myc表达的影响，并将这些结果与去甲肾上腺素的已知作用进行比较。
通过经左心房灌注将Langendorff装置转换为工作模式，获取工作大鼠心脏。使用特异性cDNA克隆，通过Northern印迹法测量c-fos和c-myc的mRNA，并通过光密度法进行定量。在用去甲肾上腺素（3×10⁻⁸ M）刺激后、后负荷从80 cm H₂O增加到100 cm H₂O以及左心房充盈压（前负荷）从8 cm H₂O增加到16 cm H₂O分别持续15、30、60、90和120分钟后从心脏中分离总RNA。
在新鲜切除的大鼠心脏中未检测到c-fos和c-myc的mRNA。当心脏以工作模式灌注15、30、60、90和120分钟时，可测量到c-fos和c-myc的mRNA，这些mRNA水平作为对照基线值设定为100%。注入去甲肾上腺素后，30分钟后c-fos mRNA增加5倍，60分钟后增加3倍，90分钟后增加3.8倍。c-myc的mRNA在60分钟后增加1.8倍，90分钟后增加3.8倍。后负荷增加在30分钟后使c-fos mRNA增加3倍，在90分钟后使c-myc mRNA增加3倍。当增加前负荷时，与对照组相比，30分钟后c-fos mRNA升高1.8倍，60分钟后c-myc mRNA升高2倍，90分钟后升高2.8倍。
压力和容量超负荷对c-fos和c-myc mRNA表达的影响与去甲肾上腺素刺激所获得的影响相似，而去甲肾上腺素刺激诱导了最明显的信号。我们的时间进程研究表明，c-fos mRNA总是在c-myc mRNA之前升高。这种共同的顺序诱导模式可能在触发心脏肥大发展的过程中具有重要的信号功能。
