Ling Q, Guo Z, Chen T, Yu Y
Laboratory of Molecular Pharmacology, Hunan Medical University, Changsha, China.
Hunan Yi Ke Da Xue Xue Bao. 1997;22(4):283-6.
To study the effects of specific angiotension II (Ang II) receptor, type-1 (AT1) antagonist (Losartan) and type-2 (AT2) antagonist (PD123319), on Ang II-induced proto-oncogene expression and synthesis of RNA and protein in neonatal rat cardiac myocytes, we used respectively [3H]-uridine and [3H]-leucine incorporation to measure the rate of RNA and protein synthesis, and analyzed the c-myc mRNA level by Northern blot. We found that an acceleration in the rate of RNA and protein synthesis was observed when exposed to 2.5 x 10(-6) mol.L-1 [Sar1] Ang II for 24 h (P < 0.01). Losartan inhibited the action in a dose-dependent manner. The level of c-myc mRNA was up-regulated to 340% of control by 2.5 x 10(-6) mol.L-1 Ang II, and Losartan (10(-5) mol.L-1) suppressed the increase of c-myc mRNA stimulated by Ang II. PD123319 showed similar inhibition on Ang II-induced RNA and protein synthesis, but did not inhibit c-myc expression. Thus, Ang II-stimulated expression of c-myc is mainly mediated by AT1 receptors, and contributes to cardiac myocyte hypertrophy while AT2 receptors are involved in mediation of cellular growth without altering of c-myc expression.
为研究特异性血管紧张素II（Ang II）1型（AT1）受体拮抗剂（氯沙坦）和2型（AT2）受体拮抗剂（PD123319）对Ang II诱导的新生大鼠心肌细胞原癌基因表达及RNA和蛋白质合成的影响，我们分别采用[3H] - 尿苷和[3H] - 亮氨酸掺入法测定RNA和蛋白质合成速率，并通过Northern印迹分析c - myc mRNA水平。我们发现，当暴露于2.5×10（-6）mol·L-1的[Sar1] Ang II 24小时时，RNA和蛋白质合成速率加快（P < 0.01）。氯沙坦以剂量依赖性方式抑制该作用。2.5×10（-6）mol·L-1的Ang II使c - myc mRNA水平上调至对照的340%，而氯沙坦（10（-5）mol·L-1）抑制了Ang II刺激的c - myc mRNA增加。PD123319对Ang II诱导的RNA和蛋白质合成表现出类似的抑制作用，但不抑制c - myc表达。因此，Ang II刺激的c - myc表达主要由AT1受体介导，并导致心肌细胞肥大，而AT2受体参与细胞生长的介导但不改变c - myc表达。
