Murrayafoline A Induces a G0/G1-Phase Arrest in Platelet-Derived Growth Factor-Stimulated Vascular Smooth Muscle Cells.
Murrayafoline A Induces a G0/G1-Phase Arrest in Platelet-Derived Growth Factor-Stimulated Vascular Smooth Muscle Cells.
复制标题
DOI：
10.4196/kjpp.2015.19.5.421
复制
发表时间：
2015-09
期刊：
影响因子：
--
通讯作者：
Myung CS
中科院分区：
文献类型：
--
作者：
Han JH;Kim Y;Jung SH;Lee JJ;Park HS;Song GY;Cuong NM;Kim YH;Myung CS
血管平滑肌细胞（VSMC）生长潜力的增加是动脉粥样硬化和血管成形术后再狭窄发展中的关键异常。血小板衍生生长因子（PDGF）的异常高活性被认为在这些病理生理情况的病因学中起着核心作用。本文研究了从芸香科植物Glycosmis stenocarpa Guillamin中提取的咔唑生物碱Murrayafoline A对PDGF-BB刺激的VSMCs增殖的抑制作用及其可能的机制。Murrayafoline A以浓度依赖性方式抑制PDGF-BB刺激的VSMC增殖，如使用非放射性比色WST-1测定和直接细胞计数所测量的。此外，通过[3 H]-胸苷掺入试验和细胞周期进展分析测定，Murrayafoline A抑制PDGF-BB刺激的细胞周期从G 0/G1期到S期的进展。在PDGF-BB刺激的VSMCs中，Murrayafoline A的这种抗增殖作用，将细胞周期进程阻滞在G 0/G1期，是通过下调细胞周期蛋白D1、细胞周期蛋白E、细胞周期蛋白依赖性激酶（CDK）2、CDK 4和增殖细胞核抗原（PCNA）的表达以及视网膜母细胞瘤蛋白（pRb）的磷酸化介导的。这些结果表明，Murrayafoline A可能有助于预防血管并发症的进展，如经皮冠状动脉腔内成形术后再狭窄和动脉粥样硬化。
The increased potential for vascular smooth muscle cell (VSMC) growth is a key abnormality in the development of atherosclerosis and post-angioplasty restenosis. Abnormally high activity of platelet-derived growth factor (PDGF) is believed to play a central role in the etiology of these pathophysiological situations. Here, we investigated the anti-proliferative effects and possible mechanism(s) of murrayafoline A, a carbazole alkaloid isolated from Glycosmis stenocarpa Guillamin (Rutaceae), on PDGF-BB-stimulated VSMCs. Murrayafoline A inhibited the PDGF-BB-stimulated proliferation of VSMCs in a concentration-dependent manner, as measured using a non-radioactive colorimetric WST-1 assay and direct cell counting. Furthermore, murrayafoline A suppressed the PDGF-BB-stimulated progression through G0/G1 to S phase of the cell cycle, as measured by [3H]-thymidine incorporation assay and cell cycle progression analysis. This anti-proliferative action of murrayafoline A, arresting cell cycle progression at G0/G1 phase in PDGF-BB-stimulated VSMCs, was mediated via down-regulation of the expression of cyclin D1, cyclin E, cyclin-dependent kinase (CDK)2, CDK4, and proliferating cell nuclear antigen (PCNA), and the phosphorylation of retinoblastoma protein (pRb). These results indicate that murrayafoline A may be useful in preventing the progression of vascular complications such as restenosis after percutaneous transluminal coronary angioplasty and atherosclerosis.