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|本期目录/Table of Contents|

三磷酸肌醇受体参与心肌钙调神经磷酸酶信号通路的激活(PDF)

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2005年第3期
页码:
220-224
栏目:
基础研究
出版日期:
2005-05-05

文章信息/Info

Title:
Inositol 1,4,5trisphosphate receptor involved in the activation of calcineurin signaling pathway in myocardium
作者:
周兴文;  杨永健;  张继红
成都军区总医院心血管内科，四川 成都 610083
Author(s):
ZHOU Xingwen;  YANG Yongjian;  ZHANG Jihong
Department of Cardiology, General Hospital of Chengdu Army, Chengdu,Sichuan 610083,China
关键词:
心肌肥厚; 信号转导; 三磷酸肌醇受体; 钙调神经磷酸酶
Keywords:
cardiac hypertrophy;  signaling transduction;  inositol 1; 4; 5trisphosphate receptor ;  calcineurin
分类号:
R541.2
DOI:
-
文献标识码:
A
摘要:
目的 研究激活心肌细胞三磷酸肌醇受体（IP3R）是否触发钙调神经磷酸酶（CaN）介导的心肌肥厚信号通路。方法 培养的乳鼠心肌细胞检测心肌细胞蛋白合成，细胞内钙变化，CaN、活化T细胞核因子3（NFAT3）及锌指转录因子（GATA4），胚胎基因（αskeletalactin,βMHC）及即刻早期基因（cfos,cmyc）蛋白表达。结果 三磷酸肌醇（IP3）能显著致原代培养的心肌细胞时间和剂量依赖性地增加心肌细胞蛋白合成，能显著致心肌细胞的早期即刻基因和胚胎基因表达,能显著增加心肌细胞内游离钙。IP3剌激IP3受体，能显著激活心肌细胞CaN/NFAT3/GATA4信号通路，使心肌细胞早期即刻基因(cfos、cmyc)及胚胎基因(αskeletalactin,βMHC)表达增加。 结论 激活IP3R介导的CaN/NFAT3/GATA4信号通路能显著地促使心肌细胞肥大，这条信号通路不同于已知的G蛋白偶联受体介导的心肌肥厚信号转导途径。
Abstract:
AIM To investigate whether the activation of InsP3R mediated calcineruin( CaN)/nuclear factor of activated Tlymphocyte3(NFAT3)/GATA4 (Zinic finger transcription factor ) pathway plays a potential role in regulation of cardiomyocyte hypertrophy and whetherheparin may antagonize this signaling pathway. METHODS Primary neonatal rat cardiomyocytes were measured using rationmetric Fura2 fluorescence. Protein synthesis of cardiomyocytes was performed by3HLeucine incorporation. Western blotting was used to evaluate the semiquantification of CaN， NFAT3， GATA4， αskeletal actin, cfos, cmyc protein expressions of CaN, NFAT3 . RTPCR was used to analyze the mRNA expression of βmyosin heavy chain. RESULTS Inositol 1,4,5trisphosphate (lnsP3) (1 nmol/L~ 1 μmol/L) caused a dosedependent increase in cytostolic free calcium concentration of cardiomyocytes. InsP3 also promoted the protein synthesis(3HLeu incorporation) of cardiomyocytes in a time and dosedependent manner. cfos, cmyc, αskeletalactin protein and βMHC mRNA expressions of cardiomyocytes were significantly enhanced by administration of InsP3. Stimulation of cardiomyocytes was also significantly enhanced by administration of InsP3. Stimulation of cardiomyocytes with InsP3 revealed a time  dependent increase in the expressions of CaN, NFAT3, and GATA4. CONCLUSION Alteration of InsP3 sensitive calcium pool can be coupled to activation of the cardiac hypertrophic gene regulatory pathways.Antagonizing InsP3R/ CaN/ NFAT3 signaling pathway may be a valuable therapeutic target for cardiac hypertrophy.

参考文献/References

［1］ Yue TL, Gu JL, Wang C, et al .Extracellular signal regulated kinase plays an essential role in hypertophic agonists, endothelin1 and phenylephrineinduced cardiomyocyte hypertrophy［J］. J Biol Chem， 2000, 275 : 37895-37901 .

［2］ Diedrichs H, Chi M, Boelck B, et al. Increased regulatory activity of the calcineruin/NFAT pathway in human heart failure［J］. Eur J Heart Fail，2004,6(1):3-9.

［3］ Wilkins BJ, Dai YS, Bueno OF, et al. Calcineruin/NFAT coupling participates in pathological, but not physiological, cardiac hypertrophy［J］. Cir Res,2004, 93(1): 111-118.

备注/Memo

备注/Memo:
收稿日期：2004-10-10.基金项目：四川省科委资助项目（2000145）
更新日期/Last Update: 2010-01-05