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1.
林瑶  牛勃  解军  颜真 《生命科学研究》2006,10(3):224-227
采用差速贴壁法体外原代培养大鼠心肌细胞;NPY刺激培养的心肌细胞增殖;RNA干涉特异性抑制CaN的活性,阻断NPY刺激的心肌细胞中Ca2 /CaM-CaN信号转导通路;观察对CaN活性、表达水平和心肌细胞蛋白合成速率的变化.实验结果显示NPY可增加心肌细胞的CaN活性和表达,加快细胞内蛋白合成速率.RNA干涉抑制CaN活性后,明显降低NPY刺激的蛋白合成速率.CaN参与了NPY刺激的心肌细胞增殖,RNA干涉通过抑制CaN的活性可阻断N PY诱导的心肌细胞肥大Ca2 /CaM-CaN通路.  相似文献   

2.
目的:研究钙调神经磷酸酶(CaN)信号通路在肿瘤坏死因子-α(TNF-α)诱导心肌细胞肥大中的作用。方法:Lowry法测心肌细胞蛋白含量;计算机图象分析系统测心肌细胞体积;[3H]-亮氨酸掺入法测心肌细胞蛋白合成;Till阳离子测定系统观察胞内[Ca2+]i瞬变;Western blot法测定CaN的表达。结果:①CaN特异性抑制剂CsA(0.2μmol/L)明显抑制TNF-α(100μg/L)诱导的心肌细胞蛋白含量、蛋白合成和细胞体积增大,但对正常心肌细胞生长无影响。②CaN特异性抑制剂CsA(0.2μmol/L)明显降低TNF-α诱导的心肌细胞内钙离子浓度([Ca2+]i)瞬变幅度增高。③TNF-α明显增强心肌细胞内CaN的表达。结论:TNF-α可能通过引起心肌细胞[Ca2+]i升高,促进CaN表达诱导心肌细胞肥大。  相似文献   

3.
目的:研究硫化氢(H2S)对心肌细胞肥大的负性调控作用与miRNA-133a介导Ca2+/CaN/NFATc4信号通路的关系。方法:异丙肾上腺素(ISO)诱导体外培养的大鼠心肌细胞肥大模型;Leica图像分析软件测量心肌细胞表面积;qRT-PCR检测脑钠尿肽(BNP)、β-肌球蛋白重链(β-MHC)、H2S合酶(CSE)、miRNA-133a和钙调神经磷酸酶(CaN) mRNA表达;Western blot检测CaN、活化T细胞核因子c4(NFATc4)蛋白表达;Elisa方法检测心肌细胞H2S含量;激光共聚焦显微镜检测心肌细胞钙离子浓度;细胞免疫荧光检测NFATc4核转位变化。结果:①心肌细胞肥大时,CSE/H2S水平、miRNA-133a mRNA表达均显著下降。应用NaHS预处理,能上调心肌细胞CSE/H2S水平,增加H2S含量和miRNA-133a mRNA表达,并明显抑制心肌细胞肥大。②心肌细胞肥大时,细胞内钙离子浓度明显增加,CaN表达和NFATc4胞核蛋白表达增加,NFATc4核转位明显增强;应用NaHS预处理能明显抑制ISO诱导的上述效应。③应用antagomir-133a能逆转H2S抑制心肌细胞肥大的作用,使心肌细胞内钙离子浓度、CaN表达和NFATc4胞核蛋白表达增加,NFATc4核转位增强。结论:H2S通过负性调控作用抑制心肌细胞肥大,该作用可能与H2S上调miRNA-133a的表达,抑制其下游的Ca2+/CaN/NFATc4信号通路的激活有关。  相似文献   

4.
Fu MG  Wang XH  Jiang ZS  Pang YZ  Liu NK  Tang CS 《生理学报》1999,51(5):597-601
本研究观察了钙调神经磷酸酶依赖的信号通路在血管紧张素Ⅱ诱导的大鼠心肌细胞肥大中的作用。在AngⅡ刺激的大鼠心肌细胞肥大模型上,应用环孢素A(CsA)阻断CaN通路,观察心肌细胞^3H-亮氨酸掺入,CaN,MAPK及PKC活性的变化。结果表明,AngⅡ(10^-7mol/L)刺激大鼠心肌细胞^3H-亮氨酸掺入较对照组增高46%(P〈0.01),CsA(0.5-5μg/ml)可以浓度依赖性方式抑制An  相似文献   

5.
Cardiac hypertrophy is a common pathological change accompanying cardiovascular disease. Recently, some evidence indicated that calcium-sensing receptor (CaSR) expressed in the cardiovascular tissue. However, the functional involvement of CaSR in cardiac hypertrophy remains unclear. Previous studies have shown that CaSR caused accumulation of inositol phosphate to increase the release of intracellular calcium. Moreover, Ca2+-dependent phosphatase calcineurin (CaN) played a vital role in the development of cardiac hypertrophy. Therefore, we investigated the expression of CaSR in cardiac hypertrophy-induced by angiotensin II (AngII) and the effects of CaSR activated by GdCl3 on the related signaling transduction pathways. The results showed that AngII induced cardiac hypertrophy and up-regulated the expression of CaSR, meanwhile increased the intracellular calcium concentration ([Ca2+]i) and activated CaN hypertrophic signaling pathway. Compared with AngII alone, the above changes were further obvious when adding GdCl3. But the effects of GdCl3 on the cardiac hypertrophy were attenuated by CsA, a specific inhibitor of CaN. In conclusion, these results suggest that CaSR is involved in cardiac hypertrophy-induced by AngII through CaN pathway in cultured neonatal rat cardiomyocytes.  相似文献   

6.
Prevention of adverse cardiac remodeling after myocardial infarction (MI) remains a therapeutic challenge. Angiotensin-converting enzyme inhibitors (ACE-I) are a well-established first-line treatment. ACE-I delay fibrosis, but little is known about their molecular effects on cardiomyocytes. We investigated the effects of the ACE-I delapril on cardiomyocytes in a mouse model of heart failure (HF) after MI. Mice were randomly assigned to three groups: Sham, MI, and MI-D (6 weeks of treatment with a non-hypotensive dose of delapril started 24h after MI). Echocardiography and pressure-volume loops revealed that MI induced hypertrophy and dilation, and altered both contraction and relaxation of the left ventricle. At the cellular level, MI cardiomyocytes exhibited reduced contraction, slowed relaxation, increased diastolic Ca2+ levels, decreased Ca2+-transient amplitude, and diminished Ca2+ sensitivity of myofilaments. In MI-D mice, however, both mortality and cardiac remodeling were decreased when compared to non-treated MI mice. Delapril maintained cardiomyocyte contraction and relaxation, prevented diastolic Ca2+ overload and retained the normal Ca2+ sensitivity of contractile proteins. Delapril maintained SERCA2a activity through normalization of P-PLB/PLB (for both Ser16- PLB and Thr17-PLB) and PLB/SERCA2a ratios in cardiomyocytes, favoring normal reuptake of Ca2+ in the sarcoplasmic reticulum. In addition, delapril prevented defective cTnI function by normalizing the expression of PKC, enhanced in MI mice. In conclusion, early therapy with delapril after MI preserved the normal contraction/relaxation cycle of surviving cardiomyocytes with multiple direct effects on key intracellular mechanisms contributing to preserve cardiac function.  相似文献   

7.
The cardiovascular benefit of fish oil in humans and experimental animals has been reported. Endothelin (ET)-1 is a well-known cardiac hypertrophic factor. However, although many studies link a fish oil extract, eicosapentaenoic acid (EPA), to cardiac protection, the effects of EPA on cardiac hypertrophy and underlying mechanism(s) are unclear. The present study investigated whether EPA prevents ET-1-induced cardiomyocyte hypertrophy; the potential pathways likely to underlie such an effect were also investigated. Cardiomyocytes were isolated from neonatal rat heart, cultured for 3 days, and then treated for 24 h with vehicle only (control), treated with 0.1 nM ET-1 only, or pretreated with 10 microM EPA and then treated with 0.1 nM ET-1. The cells were harvested, and changes in cell surface area, protein synthesis, expression of a cytoskeletal (alpha-actinin) protein, and cell signaling were analyzed. ET-1 induced a 97% increase in cardiomyocyte surface area, a 72% increase in protein synthesis rate, and an increase in expression of alpha-actinin and signaling molecule [transforming growth factor-beta 1 (TGF-beta 1), c-Jun NH2-terminal kinase (JNK), and c-Jun]. Development of these ET-1-induced cellular changes was attenuated by EPA. Moreover, the hypertrophied cardiomyocytes showed a 1.5- and a 1.7-fold increase in mRNA expression of atrial and brain natriuretic peptides, the classical molecular markers of cardiac hypertrophy, respectively; these changes were also suppressed by EPA. Here we show that ET-1 induces cardiomyocyte hypertrophy and expression of hypertrophic markers, possibly mediated by JNK and TGF-beta 1 signaling pathways. These ET-1-induced effects were blocked by EPA, a major fish oil ingredient, suggesting that fish oil may have beneficial protective effects on cardiac hypertrophy.  相似文献   

8.
Zhong X  Liu J  Lu F  Wang Y  Zhao Y  Dong S  Leng X  Jia J  Ren H  Xu C  Zhang W 《Cell biology international》2012,36(10):937-943
Nuclear Ca2+ plays a pivotal role in the regulation of gene expression. IP3 (inositol-1,4,5-trisphosphate) is an important regulator of nuclear Ca2+. We hypothesized that the CaR (calcium sensing receptor) stimulates nuclear Ca2+ release through IICR (IP3-induced calcium release) from perinuclear stores. Spontaneous Ca2+ oscillations and the spark frequency of nuclear Ca2+ were measured simultaneously in NRVMs (neonatal rat ventricular myocytes) using confocal imaging. CaR-induced nuclear Ca2+ release through IICR was abolished by inhibition of CaR and IP3Rs (IP3 receptors). However, no effect on the inhibition of RyRs (ryanodine receptors) was detected. The results suggest that CaR specifically modulates nuclear Ca2+ signalling through the IP3R pathway. Interestingly, nuclear Ca2+ was released from perinuclear stores by CaR activator-induced cardiomyocyte hypertrophy through the Ca2+-dependent phosphatase CaN (calcineurin)/NFAT (nuclear factor of activated T-cells) pathway. We have also demonstrated that the activation of the CaR increased the NRVM protein content, enlarged cell size and stimulated CaN expression and NFAT nuclear translocation in NRVMs. Thus, CaR enhances the nuclear Ca2+ transient in NRVMs by increasing fractional Ca2+ release from perinuclear stores, which is involved in cardiac hypertrophy through the CaN/NFAT pathway.  相似文献   

9.
Wu B  Wang TH  Pan JY  Zhu XN  Zhan CY 《生理学报》1998,50(1):87-93
内皮系-1(ET-1)是一种强的生长因子,并诱导心肌细胞肥大反应。在本实验中,我们探讨了G蛋白、蛋白激酶C(PKC)和Na+-H+交换在ET-1诱导的培养新生大鼠心肌细胞肥大反应中的作用。ET-1(10-10~10-7mol/L)促进3H-亮氨酸掺入,增加细胞蛋白质的含量和心肌细胞的表面积,且呈剂量依赖性,它们的EC50分别为5.2×10-10,5.2×10-10和7.3×10-10mol/L。用蛋白激酶C(PKC)抑制剂,Staurosporin(2nmol/L)预处理心肌细胞,可完全阻断ET-1诱导的心肌细胞的这些肥大反应,而蛋白激酶C激动剂,佛波酸酯(PMA)(10-8~10-6mol/L)呈剂量依赖性促进心肌细胞的肥大反应。用Na+-H+交换抑制剂,氨氯毗咪(10-4mol/L)预处理心肌细胞,可抑制ET-1诱导的心肌细胞肥大反应,但不影响PMA诱导的心肌细胞肥大反应。百日咳毒素(150ng/ml)预处理心肌细胞,可明显抑制ET-1诱导的心肌细胞肥大反应。这些结果提示,ET-1诱导的培养新生大鼠心肌细胞肥大反应是与百日咳毒素敏感的G蛋白相耦联,蛋白激酶C和Na+.H+交换可能在ET-1诱导的心肌细胞肥大反应中是重要的细胞内信使转导途径。  相似文献   

10.
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