钙调神经磷酸酶依赖的信号通路在大鼠心肌肥大中的作用及调节  被引量:10

Role and Regulation of Calcineurin dependent Signal Pathway in Cardiac Hypertrophy of Rats

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作  者:符民桂[1] 唐朝枢 

机构地区:[1]北京大学第一医院心血管研究所,北京100034 [2]不详

出  处:《生理科学进展》2001年第1期52-54,共3页Progress in Physiological Sciences

基  金:国家自然科学基金(39730220)资助课题

摘  要:本工作在大体动物模型、细胞及分子水平上 ,对钙调神经磷酸酶 (CaN)依赖的信号通路在大鼠心肌肥大中的作用及其调节机制进行了研究。结果发现 :(1)CaN信号通路参与血流动力学超负荷、心肌纤维化、旁 /自分泌因子等诱导的心肌细胞肥大 ;(2 )CaN信号通路参与血管紧张素Ⅱ(AngⅡ )及碱性成纤维细胞因子 (bFGF)诱导的心肌细胞肥大和AngII及bFGF刺激的心脏成纤维细胞增殖 ;(3)CaN通路与丝裂素活化蛋白激酶 (MAPK)及蛋白激酶C(PKC)信号途径可能存在相互联系 ;(4)CaN的活化依赖胞内Ca2 +浓度的持续升高 ,CaN的活化还受蛋白激酶磷酸化的调节 ;AngⅡ刺激心肌细胞CaNmRNA的表达显著增加 ,CaNmRNA本身的表达受Ca2 +信号及MAPK级联反应的调控。结论 :Ca2 +The present study investigated the role and regulation of calcineurin dependent signal pathway in cardiac hypertrophy of rats from the three levels of animal model, culturing cells and molecular biology.The results showed as follows: (1)Calcineurin signal pathway involves in myocyte hypertrophy induced by various factors such as hemodynamic overload, myocardial fibrosis, paracrine/ autocrine factors, etc.; (2) Calcineurin dependent signal pathway plays an important role not only in AngⅡ and bFGF induced cardiac myocyte hypertrophy but also in AngⅡ and bFGF stimulated cardiac fibroblast proliferation.(3)Calcineurin pathway may associate with MAPK and PKC pathways at several levels; (4)Activation of calcineurin depends on sustained increase of intracellular calcium concentration and is regulated by protein phosphorylation. The expression of calcineurin gene in AngⅡ stimulated myocytes might be regulated by Ca 2+ signal and MAPK cascade. In conclusion, Ca 2+ calcineurin signal pathway involves in the development of cardiac hypertrophy of rats.

关 键 词:心肌肥大 钙调神经磷酸酶 信号转导 环胞素A 

分 类 号:R542.2[医药卫生—心血管疾病]

 

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