钙调神经磷酸酶在血管紧张素II诱导的大鼠心肌细胞肥大中的作用。

Role of calcineurin in angiotensin II-induced cardiac myocyte hypertrophy of rats.

作者信息

Fu M, Zhang J, Xu S, Pang Y, Liu N, Tang C

机构信息

Institute of Cardiovascular Research, First Hospital, Beijing Medical University, Beijing 100034.

出版信息

Chin Med Sci J. 2001 Mar;16(1):1-4.

PMID:12899339

Abstract

OBJECTIVE

The present study investigated the role of calcineurin in angiotensin II(AngII) -induced cardiac myocyte hypertrophy of rats.

METHOD

The primary cardiac myocytes were cultured under the standard conditions. The calcineurin activity in AngII-treated cardiomyocytes was tested by using PNPP; protein synethsis rate was assessed by 3H-leucine incorporation; atrial natriuretic factor(ANF) mRNA level was determined by Northern blot analysis. Cell viability was estimated by lactate dehydrogenase (LDH) levels in cultured medium and by dyed cell numbers.

RESULT

After stimulation of 10, 100 and 1 000 nmol/L of AngIi, calcineurin activities in the cardiomyocytes were increased by 13%, 57% (P < 0.05) and 228% (P < 0.01) respectively, compared with control group. Cyclosporin A(CsA), a specific inhibitor of calcineurin, markedly inhibited the calcineurin activity and decreased the 3H-leucine incorporation in AngII-treated cardiomyocytes in a dose-dependent manner. It was also found that CsA slightly reduced the mRNA level of ANF gene in AngII-stimulated cardiomyocytes.

CONCLUSION

During AngII-induced cardiac myocyte hypertrophy, calcineurin signal pathway is activated, and inhibition of the pathway can attenuate AngII-induced cardiac myocyte hypertrophy, which suggests that the calcineurin signal pathway may play an important role in AngII-induced myocardial hypertrophy of rats.

摘要

目的

本研究探讨钙调神经磷酸酶在血管紧张素II（AngII）诱导的大鼠心肌细胞肥大中的作用。

方法

在标准条件下培养原代心肌细胞。用对硝基苯磷酸酯（PNPP）检测AngII处理的心肌细胞中钙调神经磷酸酶的活性；通过3H-亮氨酸掺入评估蛋白质合成率；用Northern印迹分析测定心钠素（ANF）mRNA水平。通过培养基中乳酸脱氢酶（LDH）水平和染色细胞数量评估细胞活力。

结果

与对照组相比，在10、100和1000 nmol/L的AngII刺激后，心肌细胞中钙调神经磷酸酶的活性分别增加了13%、57%（P<0.05）和228%（P<0.01）。钙调神经磷酸酶的特异性抑制剂环孢素A（CsA）以剂量依赖的方式显著抑制钙调神经磷酸酶的活性，并降低AngII处理的心肌细胞中3H-亮氨酸的掺入。还发现CsA略微降低了AngII刺激的心肌细胞中ANF基因的mRNA水平。