Komuro I, Kaida T, Shibazaki Y, Kurabayashi M, Katoh Y, Hoh E, Takaku F, Yazaki Y
Third Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
J Biol Chem. 1990 Mar 5;265(7):3595-8.
Recently cellular protooncogenes have been found to be induced as an early response to pressure overload in cardiac hypertrophy. To examine whether mechanical stimuli directly induce specific gene expression in the heart, we cultured rat neonatal cardiocytes in elastic silicone dishes and stretched these adherent cells. Myocyte stretching stimulated expression of the protooncogene, c-fos, in a stretch length-dependent manner, followed by an increase in amino acid incorporation into proteins. c-fos mRNA levels were enhanced within 15 min by cardiocyte stretching, peaked at 30 min, and declined to undetectable levels by 240 min. In the presence of cycloheximide, a greater increase in c-fos mRNA was seen by stretching. The transfected chloramphenicol acetyltransferase gene linked to upstream sequences of the fos gene including its promoter was also activated by stretching cardiac myocytes. These results suggest that mechanical loading directly regulates gene transcription without the participation of humoral factors in cardiocytes.
最近发现细胞原癌基因作为心脏肥大时压力超负荷的早期反应被诱导。为了研究机械刺激是否直接诱导心脏中的特定基因表达，我们将大鼠新生心肌细胞培养在弹性硅胶培养皿中，并拉伸这些贴壁细胞。心肌细胞拉伸以拉伸长度依赖的方式刺激原癌基因c-fos的表达，随后蛋白质中氨基酸掺入增加。心肌细胞拉伸在15分钟内增强了c-fos mRNA水平，在30分钟达到峰值，并在240分钟时降至不可检测水平。在放线菌酮存在的情况下，拉伸可使c-fos mRNA有更大程度的增加。与fos基因上游序列（包括其启动子）相连的转染氯霉素乙酰转移酶基因也被心肌细胞拉伸激活。这些结果表明，机械负荷直接调节心肌细胞中的基因转录，而无需体液因子的参与。
