王艳春 关凤英 李红 杨世杰 . 牛磺酸通过抑制PKCα抗心肌成纤维细胞增殖的作用J. 药学学报, 2009,44(6): 591-596.
引用本文: 王艳春 关凤英 李红 杨世杰 . 牛磺酸通过抑制PKCα抗心肌成纤维细胞增殖的作用J. 药学学报, 2009,44(6): 591-596.
WANG Yan-Chun, GUAN Feng-Yang, LI Gong, YANG Shi-Jie- . Anti-proliferation action of taurine on rat cardiac fibroblast through inhibiting protein kinase Cα expressionJ. 药学学报, 2009,44(6): 591-596.
Citation: WANG Yan-Chun, GUAN Feng-Yang, LI Gong, YANG Shi-Jie- . Anti-proliferation action of taurine on rat cardiac fibroblast through inhibiting protein kinase Cα expressionJ. 药学学报, 2009,44(6): 591-596.

牛磺酸通过抑制PKCα抗心肌成纤维细胞增殖的作用

Anti-proliferation action of taurine on rat cardiac fibroblast through inhibiting protein kinase Cα expression

  • 摘要:

    观察牛磺酸 (taurine, Tau) 在血管紧张素Ⅱ (angiotensinⅡ, AngⅡ) 诱导新生大鼠心肌成纤维细胞 (cardiac fibroblast, CFb) 增殖过程中对细胞周期调控蛋白p27Cyclin D1及核因子-κB (NF-κB) p65的影响, 以探讨牛磺酸抑制CFb增殖的途径。胰酶消化法分离培养新生大鼠CFb, AngⅡ诱导促进其增殖, 采用四甲基偶氮唑盐 (MTT) 法检测细胞增殖; Western blotting法检测p-PKCα含量; 流式细胞仪检测细胞周期调控蛋白p27表达; 免疫细胞化学染色检测Cyclin D1蛋白表达; 免疫荧光细胞化学染色法检测NF-κB p65蛋白的核表达。牛磺酸 (80160 mmol·L−1) 可明显抑制p-PKCα的蛋白表达。牛磺酸 (80 mmol·L−1) 可增加p27的蛋白表达 (P < 0.05); 明显抑制NF-κB p65的核转位, AngⅡ模型组比较差异具有统计学意义 (P < 0.01), 而以上作用均是通过抑制PKCα在胞膜的表达而实现的, PKC抑制剂与Tau合用呈现协同作用。牛磺酸通过抑制p-PKCα的表达而增加p27的蛋白表达、抑制NF-κB p65的核转位, 从而抑制CFb的增殖。

     

    Abstract:

    This project aimed to investigate the effect of taurine on cell cycle regulatory protein p27, Cyclin D1 and nuclear factor-kappa B (NF-κB) p65 in the proliferation of cultured neonatal rat cardiac fibroblast (CFb) induced by angiotensinⅡ (AngⅡ), and to explore the effect of taurine on the signal transduction pathway in CFb proliferation.  The cultured neonatal rat CFbs were isolated by trypsin digestion method.  The proliferation of CFb was induced by Ang Ⅱ and detected with thiazole blue (MTT) colorimetric assay.  The protein expression of p-PKCα in cells was determined with Western blotting technology.  The expression of p27 was analyzed by flow cytometry.  The expression of Cyclin D1 was determined with the combination of immunocytochemical staining and image analysis software.  The nuclear translocation of NF-κB p65 was determined with immunofluorescence staining.  Among the concentrations ranged from 40 to 160 mmol·L−1, taurine significantly inhibited p-PKCα  expression.  Taurine increased p27 expression and inhibited the nuclear translocation of NF-κB p65 in CFb   (P < 0.05, P < 0.01, respectively) by inhibition of p-PKCα expression.  And PKC inhibitor (Che) could improve the inhibitory action of taurine on CFb proliferation.  The effects of taurine on CFb proliferation might be due  to inhibition of p-PKCα expression and p27 expression increase and the nuclear translocation of NF-κB p65   inhibition followed.

     

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