Department of Anesthesiology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan.
Acta Pharmacol Sin. 2011 Nov;32(11):1337-44. doi: 10.1038/aps.2011.105. Epub 2011 Sep 5.
To examine the inhibitory actions of the immunoregulator platonin against proliferation of rat vascular smooth muscle cells (VSMCs).
VSMCs were prepared from the thoracic aortas of male Wistar rats. Cell proliferation was examined using MTT assays. Cell cycles were analyzed using flow cytometry. c-Jun N-terminal kinase (JNK)1/2, extracellular signal-regulated kinase (ERK)1/2, AKT, and c-Jun phosphorylation or p27 expression were detected using immunoblotting.
Pretreatment with platonin (1-5 μmol/L) significantly suppressed VSMC proliferation stimulated by PDGF-BB (10 ng/mL) or 10% fetal bovine serum (FBS), and arrested cell cycle progression in the S and G(2)/M phases. The same concentrations of platonin significantly inhibited the phosphorylation of JNK1/2 but not ERK1/2 or AKT in VSMCs stimulated by PDGF-BB. Furthermore, platonin also attenuated c-Jun phosphorylation and markedly reversed the down-regulation of p27 expression after PDGF-BB stimulation.
Platonin inhibited VSMC proliferation, possibly via inhibiting phosphorylation of JNK1/2 and c-Jun, and reversal of p27 down-regulation, thereby leading to cell cycle arrest at the S and G(2)/M phases. Thus, platonin may represent a novel approach for lowering the risk of abnormal VSMC proliferation and related vascular diseases.
研究免疫调节剂褪黑素对大鼠血管平滑肌细胞（VSMCs）增殖的抑制作用。
从雄性 Wistar 大鼠的胸主动脉中分离出 VSMCs。使用 MTT 法检测细胞增殖。通过流式细胞术分析细胞周期。使用免疫印迹法检测 c-Jun N 末端激酶（JNK）1/2、细胞外信号调节激酶（ERK）1/2、AKT 的磷酸化或 p27 的表达。
褪黑素（1-5 μmol/L）预处理可显著抑制 PDGF-BB（10ng/mL）或 10%胎牛血清（FBS）刺激的 VSMC 增殖，并将细胞周期阻滞在 S 和 G2/M 期。相同浓度的褪黑素可显著抑制 PDGF-BB 刺激的 VSMCs 中 JNK1/2 的磷酸化，但不抑制 ERK1/2 或 AKT 的磷酸化。此外，褪黑素还可减弱 c-Jun 的磷酸化，并显著逆转 PDGF-BB 刺激后 p27 表达的下调。
褪黑素抑制 VSMC 增殖，可能是通过抑制 JNK1/2 和 c-Jun 的磷酸化以及 p27 表达的下调，从而导致 S 和 G2/M 期的细胞周期阻滞。因此，褪黑素可能为降低异常 VSMC 增殖和相关血管疾病的风险提供了一种新的方法。
