Watson P A, Hannan R, Carl L L, Giger K E
Weis Center for Research, Geisinger Clinic, Danville, Pennsylvania 17822-2615, USA.
Am J Physiol. 1996 Apr;270(4 Pt 1):C1228-35. doi: 10.1152/ajpcell.1996.270.4.C1228.
Experiments were performed to assess the ability of mechanical stimuli, experienced by ventricular cardiac myocytes during the progression of hypertrophic and dilated pathology, to increase the expression of desmin in cultured neonatal rat cardiac myocytes. Results indicate that both contractile activity and load due to passive stretch increase desmin content in neonatal rat cardiac myocytes through increased desmin gene transcription. Western blot analysis demonstrated that contraction induced a selective increase in desmin protein content in neonatal rat cardiac myocytes above increases observed in the content of total cellular protein. Northern blot analysis indicated that desmin mRNA content increased in response to contraction as well as to alpha-adrenergic stimulation. Desmin mRNA content also increased in cultured neonatal myocytes in response to stretch. Angiotensin II (ANG II) treatment of contracting neonatal cardiac myocytes further increased desmin mRNA content, whereas similar treatment in arrested neonatal cardiac myocytes further increased desmin mRNA content, whereas similar treatment in arrested neonatal cardiac myocytes failed to increase desmin mRNA. This contraction-dependent responsiveness to ANG II is not a function of increases in the density or relative subtype composition of ANG II receptors. Treatment of contracting neonatal rat cardiac myocytes with actinomycin D prevented increases in desmin mRNA content, suggesting regulation of transcription of the desmin gene by contraction. Nuclear run-on experiments indicate that contraction. Nuclear run-on experiments indicate that contraction increases transcription of the desmin gene in cardiac myocytes. These results are consistent with the modulation of desmin gene expression secondarily to changes in the mechanical environment that occur in cardiac tissue undergoing dilation or hypertrophy.
进行实验以评估肥厚性和扩张性病变进展过程中心室心肌细胞所经历的机械刺激增加培养的新生大鼠心肌细胞中结蛋白表达的能力。结果表明，收缩活动和被动拉伸引起的负荷均通过增加结蛋白基因转录来增加新生大鼠心肌细胞中的结蛋白含量。蛋白质印迹分析表明，收缩导致新生大鼠心肌细胞中结蛋白蛋白含量选择性增加，高于总细胞蛋白含量的增加。Northern印迹分析表明，结蛋白mRNA含量响应收缩以及α-肾上腺素能刺激而增加。结蛋白mRNA含量在培养的新生心肌细胞中对拉伸也有增加。用血管紧张素II（ANG II）处理收缩的新生心肌细胞进一步增加了结蛋白mRNA含量，而在静止的新生心肌细胞中进行类似处理未能增加结蛋白mRNA。这种对ANG II的收缩依赖性反应不是ANG II受体密度或相对亚型组成增加的作用。用放线菌素D处理收缩的新生大鼠心肌细胞可防止结蛋白mRNA含量增加，提示收缩对结蛋白基因转录有调节作用。核转录实验表明收缩。核转录实验表明收缩增加心肌细胞中结蛋白基因的转录。这些结果与在经历扩张或肥大的心脏组织中机械环境变化继发的结蛋白基因表达调节一致。
