Messina J L
Department of Physiology, SUNY Health Science Center at Syracuse 13210.
J Cell Physiol. 1994 Aug;160(2):287-94. doi: 10.1002/jcp.1041600210.
Insulin exerts rapid effects on cellular metabolism and can cause morphological changes by inducing rearrangements of cytoskeletal components. The regulation of specific cytoskeletal genes by insulin, however, has not been studied extensively. In the present work insulin was found to rapidly, but transiently, increase transcription of the cytoskeletal gamma-actin gene in rat H4IIE (H4) hepatoma cells. Insulin-induced transcription of the gamma-actin gene was evident within 5 min and was maximal by 15 min at 10-fold above control levels. The stimulation of transcription was transient, with a return towards basal levels by 120 min. Transcription of gamma-actin was increased at insulin concentrations as low as 1 x 10(-11) M and was maximal at 1 x 10(-9) to 1 x 10(-8) M. Transcription of several control genes (skeletal and cardiac alpha-actin and beta-tubulin) were unaltered by insulin administration. Messenger RNA (mRNA) levels for the gamma-actin gene increased, but to a lesser degree than transcription. Since the gamma-actin message is an abundant and stable mRNA, its levels would not be expected to change dramatically from a transient induction of transcription. Like insulin, phorbol esters transiently increased transcription of the gamma-actin gene. In addition, pretreatment of cells with phorbol esters for 24 h reduced the ability of insulin to induce gamma-actin transcription. These data support our hypothesis that insulin and phorbol esters share intracellular signalling pathways in the control of transcription of specific genes.
胰岛素对细胞代谢具有快速作用，并可通过诱导细胞骨架成分的重排引起形态变化。然而，胰岛素对特定细胞骨架基因的调控尚未得到广泛研究。在本研究中，发现胰岛素能快速但短暂地增加大鼠H4IIE（H4）肝癌细胞中细胞骨架γ-肌动蛋白基因的转录。胰岛素诱导的γ-肌动蛋白基因转录在5分钟内即可显现，15分钟时达到最大值，比对照水平高10倍。转录刺激是短暂的，120分钟时恢复到基础水平。γ-肌动蛋白的转录在低至1×10⁻¹¹ M的胰岛素浓度下即增加，在1×10⁻⁹至1×10⁻⁸ M时达到最大值。给予胰岛素后，几个对照基因（骨骼肌和心肌α-肌动蛋白以及β-微管蛋白）的转录未发生改变。γ-肌动蛋白基因的信使核糖核酸（mRNA）水平有所增加，但程度小于转录增加。由于γ-肌动蛋白信使是一种丰富且稳定的mRNA，因此预期其水平不会因转录的短暂诱导而发生显著变化。与胰岛素一样，佛波酯可短暂增加γ-肌动蛋白基因的转录。此外，用佛波酯预处理细胞24小时可降低胰岛素诱导γ-肌动蛋白转录的能力。这些数据支持了我们的假设，即胰岛素和佛波酯在控制特定基因转录方面共享细胞内信号通路。
