胰岛素样生长因子-1对血管平滑肌细胞PI3K/PTEN信号通路的影响

被引:2
作者
吴兴利
杨丁友
杨中苏
王士雯
赵玉生
机构
[1] 解放军总医院老年心血管病研究所,解放军总医院老年心血管病研究所,解放军总医院老年心血管病研究所,解放军总医院老年心血管病研究所,解放军总医院老年心血管病研究所北京,北京,北京,北京,北京
关键词
磷脂酰肌醇-3激酶; PTEN; 胰岛素样生长因子-1; 血管平滑肌细胞;
D O I
10.13459/j.cnki.cjap.2004.03.019
中图分类号
R341 [];
学科分类号
1001 ;
摘要
目的 :探讨胰岛素样生长因子 1(IGF 1)促血管平滑肌细胞 (VSMC)增殖的细胞内信号转导机制。方法 :体外培养的兔血管平滑肌细胞分 3组处理 ,以细胞计数、噻唑盐比色法测定细胞增殖能力 ,以磷脂酰肌醇 3激酶 (PI3 K)特异性抑制剂渥漫青霉素 (WT)孵育细胞间接反映PI3 K作用。WesternBlot定量磷酸酶PTEN表达水平 ,免疫沉淀、特异底物diC16PIP3 绿色试剂法测定PTEN脂质磷酸酶活性。结果 :IGF 1(10 0 μg/L)使细胞计数及MTT比色A值分别增加至对照组的 2 .8倍和 3.8倍 ,WT抑制VSMC增殖 ,并完全逆转IGF 1的作用 (均P <0 .0 1)。各浓度IGF 1对PTEN蛋白表达水平无明显影响 ,其对PTEN活性的抑制呈浓度 (10~ 10 0 μg/L)及时间 (3min~ 2 4h)依赖性 (均P <0 .0 1)。结论 :IGF 1促VSMC增殖作用与活化PI3 K蛋白激酶的促生长活性及抑制PTEN脂质磷酸酶的负性调节细胞生长作用有关
引用
收藏
页码:52 / 55
页数:4
相关论文
共 10 条
[1]  
A PI3K/Akt/mTOR pathway mediates and PTEN antagonize tumor necrosis factor inhibition of insulin signaling through insulin receptor substrate-1. Ozes O N,Akca H,Mayo L D,et al. Proceedings of the National Academy of Sciences of the United States of America . 2001
[2]  
Protein phosphatase 2A: who shall regulate the regulator. Goldberg Y. Biochemical Pharmacology . 1999
[3]  
Growth factors and atherosclerosis. Clemmons D R. Diabete Rev . 1997
[4]  
The synergistic effect of PDGF-AA and IGF-1 on SMC proliferation might be explained by the differential activation of their intracellular signaling pathways. Thommes K B,Hoppe J,Vetter H,et al. Experimental Cell Research . 1996
[5]  
Differential effects of insulin-like growth factor 1(IGF-1) and IGF-1-binding protein-1 on protein metabolism in human skeletan muscle cells. Frost R S,Lang C H. The Journal of Endocrinology . 1999
[6]  
The phosphatidylinositol 3-kinase pathway in a dominant growth factor activated cell survival pathway in LNCaP human prostate carcinoma cells. Lin J,Adam R M,Santiestevan E,et al. Cancer Research . 1999
[7]  
PTEN/MMAC1 mutation in hepatocellular carcinomas. YaoY J,Li P X,Zhang H,et al. Oncegene . 1999
[8]  
Protein kinases and protein phosphatase: the Yin and Yang of protein phosphorylation and signaling. Cohen P. Cell . 1995
[9]  
Modulation of hypoxia-inducible factor 1a expression by the epidermal growth factor PI3 K/PTEN/AKT/FRAP pathway in human prostate cancer cell: implication for tumor angiogenesis and therapeutics. Zhong H,Chiles K,Feldser D,et al. Cancer Research . 2000
[10]  
Activation of Akt/protein kinase B after stimulation with angiotensin II in vascular smooth muscle cells. Takahashi T,Taniguchi T,Konishi H,et al. American Journal of Physiology . 1999