THE EXPRESSION AND FUNCTION OF G-PROTEINS IN EXPERIMENTAL INTIMAL HYPERPLASIA
THE EXPRESSION AND FUNCTION OF G-PROTEINS IN EXPERIMENTAL INTIMAL HYPERPLASIA
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DOI：
10.1172/jci117513
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发表时间：
1994-10-01
影响因子：
15.9
通讯作者：
HAGEN, PO
中科院分区：
文献类型：
--
作者：
DAVIES, MG;RAMKUMAR, V;HAGEN, PO
G蛋白是一种膜结合的信号转导蛋白，将细胞外受体信号偶联到各种效应器上。本研究检测了G蛋白(α(I)、αS、α(Q)和α(O))在实验性内膜增生中的表达和功能。30只新西兰大白兔行静脉搭桥术，28d后取材，对侧颈静脉作为对照。对来自静脉和移植物的血管环进行了等长张力研究(n=10)，并对另外20条血管进行了Western印迹和mRNA分析。与静脉相比，移植静脉中α(Q)的表达增加了5倍，α(I2)的表达增加了2.7倍，α(S)的表达增加了3.3倍。α(I3)在静脉移植物中可检测到表达，但在颈静脉中未见表达。此外，与静脉相比，静脉移植物中的β亚基增加了3.8倍。移植静脉中α(S)、α(I3)和α(I2)基因的表达均升高。在静脉或静脉移植物中都没有检测到阿尔法(I1)蛋白或其mRNA的水平。百日咳毒素不抑制静脉收缩反应。与静脉相比，静脉移植物对去甲肾上腺素的收缩反应增强了一倍，对5-羟色胺的反应从头开始发展。静脉移植物对去甲肾上腺素和5-羟色胺的收缩反应仅被百日咳毒素部分抑制，尽管静脉和移植物中100%与百日咳毒素发生ADP核糖基化。这些数据表明，在体内，随着百日咳毒素敏感性收缩反应的发展，G-蛋白的表达增加或新的表达与内膜增生有关。G蛋白在转录水平或RNA稳定性水平上的变化可能参与了平滑肌细胞对损伤和内膜增生形成的反应。
G-proteins are membrane-bound signal transduction proteins which couple extracellular receptor signals to various effecters. This study examines the expression and the function of G-proteins (alpha(i), alpha s, alpha(q), and alpha(o)) in experimental intimal hyperplasia. Vein bypass grafts were placed in 30 New Zealand White rabbits and were harvested after 28 d. The contralateral jugular veins served as controls. Isometric tension studies were performed on rings from veins and vein grafts (n = 10), and Western blot and mRNA analyses were performed in another 20 vessels. There was a fivefold increase in alpha(q), a 2.7-fold increase in the alpha(i2), and a 3.3-fold increase in alpha(s) expressions in vein grafts compared with veins. Detectable expression of alpha(i3) was observed in vein grafts but not in jugular veins. In addition, there was a 3.8-fold increase in beta subunits in the vein grafts compared with the veins. mRNA for alpha(s), alpha(i3), and alpha(i2) were all elevated in the vein grafts. No detectable levels of the alpha(i1) protein or its mRNA were present in either veins or vein grafts. Contractile responses in the veins were not inhibited by pertussis toxin. The contractile responses to norepinephrine were enhanced by twofold, and the responses to serotonin developed de novo in vein grafts compared with veins. The contractile responses to both norepinephrine and serotonin were only partially inhibited by pertussis toxin in the vein grafts even though there was 100% ADP ribosylation with pertussis toxin in both veins and vein grafts. These data suggest that intimal hyperplasia is associated with increased or novel expression of G-proteins in vivo which occur simultaneously with the development of pertussis toxin-sensitive contractile responses. Changes in G-proteins at a transcriptional level or at the level of RNA stability may be involved in the response of smooth muscle cells to injury and to intimal hyperplasia formation.