钙激动剂介导血管平滑肌细胞增殖的信号转导途径

Signaling Pathway Mediated Cultured Vascular Smooth Muscle Cells Proliferation by Calcium Activator

为探讨钙调神经磷酸酶依赖的信号通路在雷尼丁剌激的大鼠血管平滑肌细胞增殖中的作用 ,以培养的大鼠血管平滑肌细胞为模型 ,用雷尼丁剌激其内贮Ca2 + 释放入胞浆 ,环孢素A阻断钙调神经磷酸酶信号通路 ,维拉帕米阻断钙通道 ,检测血管平滑肌细胞钙调神经磷酸酶、丝裂素活化蛋白激酶和蛋白激酶C活性 ,用 3 H -亮氨酸及3 H -胸腺嘧啶掺入量作为反应细胞增殖的指标。结果显示 ,雷尼丁剌激组蛋白核酸合成速率明显增高 ,与对照组相比差异显著 (P <0 .0 1) ;环孢素A及维拉帕米能明显抑制雷尼丁介导的平滑肌细胞蛋白核酸合成速率增高 ,与雷尼丁剌激组相比差异显著 (P <0 .0 1)。同时发现雷尼丁剌激组钙调神经磷酸酶、蛋白激酶C活性与对照组平滑肌细胞相比差异显著 (P <0 .0 5或 0 .0 1)。环孢素A和维拉帕米抑制雷尼丁介导的平滑肌细胞钙调神经磷酸酶活性增高 ,维拉帕米抑制雷尼丁介导的平滑肌细胞蛋白激酶C活性的增高。提示钙调神经磷酸酶信号通路在雷尼丁剌激的平滑肌细胞增殖中起重要作用 ,但钙调神经磷酸酶信号通路不是雷尼丁介导平滑肌细胞增殖的唯一信号通路 ,以丝裂素活化蛋白激酶为核心的信号通路亦参与了雷尼丁剌激的平滑肌细胞增殖。

Aim To study the effect of calcineurin (CaN)-dependent signaling passway on proliferation of rat vascular smooth muscle cells(VSMC) under stimulation of Ryanodine (RY). Methods Upon the model of cultured rat VSMC, Ca 2+ releasing from Ca 2+ stores stimulated with RY, CaN signaling pathway was blocked with cyclosporine A (CsA) and Ca 2+ channel with verapamil(Ver), detecting the activities of VSMC CaN, mitogen activated protein kinase (MAPK) and protein kinase C(PKC), 3 H-Leucine( 3 H-Leu) and 3 H-Thymidine( 3 H-TdR) incorporation as the target to evaluate VSMC proliferation. Results Synthesis rate of protein and nucleic acid stimulated by RY in VSMC increased significantly in contrast to control (P<0.01); CsA and Ver markedly inhibited syntheses of protein and nucleic acid mediated by RY in VSMC with a significant difference from RY-stimulated group(P<0.01). CsA and Ver also suppressed VSMC CaN activity mediated by RY, and Ver suppressed VSMC PKC activity mediated by RY. Conclusions The study indicates CaN signaling pathway play an important role in VSMC proliferation induced by RY, but it is not the only signaling pathway in regulating VSMC proliferation, MAPK-centered signaling pathway is also involved in VSMC proliferation induced by RY.