Analysis of lysophophatidylcholine-induced endothelial dysfunction.
Analysis of lysophophatidylcholine-induced endothelial dysfunction.
复制标题
溶血磷脂酰胆碱诱导的内皮功能障碍的分析。
DOI：
10.1097/00005344-199609000-00001
复制
发表时间：
1996
影响因子：
3
通讯作者：
Flavahan,NA
中科院分区：
文献类型：
--
作者：
Freeman,JE;Kuo,WY;Drenger,B;Barnett,TN;Levine,MA;Flavahan,NA
由早期动脉粥样硬化过程或由内皮暴露于致动脉粥样硬化脂质（包括溶血磷脂酰胆碱（lysoPC））引起的内皮功能障碍的特征在于由百日咳毒素敏感性G i-2蛋白介导的应答的选择性损害。进行实验以分析这种效应的机制。缓激肽（BK：G i-2蛋白非依赖性）、5-羟色胺（5-HT：G i-2蛋白依赖性）或Mastoparan直接激活G i-2蛋白可增加猪动脉内皮细胞（EC）释放内皮源性一氧化氮（EDNO）。LysoPC可减少5-HT引起的EDNO释放，但不影响BK或mastoparan的反应。LysoPC没有增加超氧自由基的产生，光泽精增强化学发光检测。Western blot分析显示对照和lysoPC处理的细胞之间的免疫反应性Gi α-2水平没有差异。通过α 2肾上腺素能受体或α 2肾上腺素能受体刺激激活Gi-2蛋白，可降低百日咳毒素催化的对照细胞膜中Gi α-2蛋白的ADP-核糖基化，但对lysoPC处理的细胞膜无影响。然而，Mastoparan对Gi-2蛋白的直接活化抑制了来自对照和lysoPC处理的细胞的膜中的ADP-核糖基化。毒素催化的反应在lysoPC处理的细胞或lysoPC处理的膜中减少。LysoPC降低了内皮素增加GTPγS与Gi-2蛋白结合的能力，但不影响mastoparan的活性。这些结果表明，lysoPC通过与受体：G1 -2-蛋白解偶联一致的作用抑制EC中的百日咳毒素敏感性信号传导途径。
Endothelial dysfunction caused by the early atherosclerotic process or by endothelial exposure to atherogenic lipids, including lysophosphatidylcholine (lysoPC), is characterized by a selective impairment of responses mediated by the pertussis toxin-sensitive G i-2 protein. Experiments were performed to analyze the mechanisms underlying this effect. Bradykinin (BK: G i-2 protein-independent), serotonin (5-HT: G i-2 protein-dependent), or direct activation of the G i-2-protein by mastoparan increased the release of endothelium-derived nitric oxide (EDNO) from porcine arterial endothelial cells (EC). LysoPC decreased the release of EDNO caused by 5-HT, but did not affect the response to BK or mastoparan. LysoPC did not increase production of superoxide radicals detected by lucigenin-enhanced chemiluminescence. Western blot analysis showed no difference in the level of immunoreactive G iα-2 between control and lysoPC-treated cells. Activation of the G i-2 protein by serotonergic or α 2-adrenoceptor stimulation decreased the pertussis toxin-catalyzed ADP-ribosylation of G iα-2 protein in membranes from control but not lysoPC-treated cells. However, direct activation of the G i-2 protein by mastoparan inhibited the ADP-ribosylation in membranes from control and lysoPC-treated cells. The toxin-catalyzed reaction was reduced in lysoPC-treated cells or lysoPC-treated membranes. LysoPC reduced the ability of endothelin to increase GTPγS binding to the G i-2 protein but did not affect the activity of mastoparan. These results suggest that lysoPC inhibits a pertussis toxin-sensitive signaling pathway in EC by an effect consistent with receptor: G i-2-protein uncoupling.