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目的 探讨不同来源的细胞内Ca2 + ([Ca2 + ]i)在钙调神经磷酸酶 (CaN) 活化T细胞核因子 3 (NFAT3 )介导的心肌肥大中的作用。方法 分别用血管紧张素Ⅱ (AngⅡ )或雷尼丁刺激培养的大鼠心肌细胞外Ca2 + 跨膜内流或细胞内Ca2 + 释放 ,检测CaN、NFAT3、锌指转录因子 (GATA4)蛋白量、NFAT3定位以及氚 亮氨酸 (3H Leu)掺入量 ,环孢素A作为CaN特异抑制剂。结果 AngⅡ、雷尼丁刺激 1、3d ,心肌细胞CaN、NFAT3、GATA4蛋白表达及3H Leu掺入量较对照组明显增高(P值 <0 0 5或 <0 0 1)。AngⅡ和雷尼丁刺激第 1天 ,心肌细胞NFAT3表达由胞质转入胞核表达为主。环孢素A可抑制上述作用 ,与刺激组相比差异有显著性 (P <0 0 5或 <0 0 1)。结论 刺激心肌细胞Ca2 + 内流及Ca2 + 释放 ,均可激活CaN NFAT3信号通路。CaN NFAT3信号通路的激活与[Ca2 + ]i增加有关 ,而与 [Ca2 + ]i的来源无关。环孢素A能够抑制AngⅡ和雷尼丁介导的CaN NFAT 3 GATA 4表达的增加和蛋白质合成
Objective To investigate the role of intracellular Ca2 + ([Ca2 +] i) from different sources in cardiac myocyte hypertrophy induced by calcineurin (CaN) activated T cell nuclear factor 3 (NFAT3). Methods The expressions of CaN, NFAT3 and GATA4 were detected by extracellular Ca2 + transmembrane influx or intracellular Ca2 + release from cultured cardiomyocytes with or without angiotensin Ⅱ (AngⅡ) NFAT3 localization and tritiated leucine (3H Leu) incorporation, cyclosporin A as CaN specific inhibitor. Results The Ang Ⅱ and Ranitidine stimulated 1,3d, CaN, NFAT3 and GATA4 protein expression and 3H-Leu incorporation in cardiomyocytes were significantly higher than those in control group (P <0.05 or <0.01). On the 1st day after stimulation with Ang II and ranitidine, the expression of NFAT3 in cardiomyocytes changed from cytoplasm to nucleus. Cyclosporine A can inhibit the above effects, compared with the stimulation group, the difference was significant (P <0 05 or <0 0 1). Conclusion Ca2 + influx and Ca2 + release from cardiomyocytes can activate CaN NFAT3 signaling pathway. Activation of CaN NFAT3 signaling is associated with an increase in [Ca2 +] i, independent of the source of [Ca2 +] i. Cyclosporine A inhibits Ang II and ranitidine-mediated increases in CaN NFAT 3 GATA 4 expression and protein synthesis