Lysophosphatidylcholine modifies G protein-dependent signaling in porcine endothelial cells.
Lysophosphatidylcholine modifies G protein-dependent signaling in porcine endothelial cells.
复制标题
溶血磷脂酰胆碱可改变猪内皮细胞中 G 蛋白依赖性信号传导。
DOI：
10.1152/ajpheart.1993.264.3.h722
复制
发表时间：
1993
期刊：
影响因子：
--
通讯作者：
Flavahan,NA
中科院分区：
文献类型：
--
作者：
Flavahan,NA
某些内皮受体偶联到百日咳毒素敏感抑制鸟嘌呤核苷酸结合调节（Gi）蛋白。在猪中，高胆固醇血症导致这种Gi蛋白依赖途径的选择性损伤。最近的研究表明高胆固醇血症引起的内皮功能障碍可能是由氧化低密度脂蛋白（LDL）衍生的溶血磷脂酰胆碱（LPC）引起的。本研究的目的是确定LPC是否可以抑制Gi蛋白依赖途径。将分离的猪冠状动脉环悬浮在充满生理盐溶液（37℃，95% O2-5% CO2）的器官室中，进行等距张力记录。在内皮因前列腺素F2 α而收缩的环中，百日咳毒素（100 ng/ml）或LPC （10(-5) M）抑制uk - 14304 （α 2-肾上腺素能激动剂）或5 -羟色胺引起的内皮依赖性松弛，但对缓激素或ADP引起的松弛无抑制作用。LPC也不抑制由内皮来源的舒张因子一氧化氮供体sin1产生的舒张。经百日咳毒素处理后，LPC不再抑制内皮依赖性血清素松弛。虽然LPC抑制了激活百日咳毒素敏感Gi蛋白的膜结合受体的反应，但LPC不影响氟直接激活百日咳毒素敏感Gi蛋白所引起的内皮依赖性松弛。这些结果表明，LPC可能通过破坏受体- g蛋白相互作用来选择性抑制猪内皮细胞中Gi蛋白依赖的途径。与氧化LDL相关的LPC可能部分介导与高胆固醇血症相关的内皮Gi蛋白依赖途径的功能障碍。
Certain endothelial receptors are coupled to a pertussis toxin-sensitive inhibitory guanine nucleotide-binding regulatory (Gi) protein. In pigs, hypercholesterolemia causes a selective impairment of this Gi protein-dependent pathway. Recent studies have suggested that hypercholesterolemia-induced endothelial dysfunction may be caused by lysophosphatidylcholine (LPC) derived from oxidized low-density lipoprotein (LDL). The aim of the present study was to determine whether LPC could inhibit the Gi protein-dependent pathway. Isolated rings of porcine coronary arteries were suspended for isometric tension recording in organ chambers filled with physiological salt solution (37 degrees C, 95% O2-5% CO2). In rings with endothelium contracted with prostaglandin F2 alpha, pertussis toxin (100 ng/ml) or LPC (10(-5) M) inhibited the endothelium-dependent relaxations evoked by UK-14,304, an alpha 2-adrenergic agonist, or by serotonin, but not those caused by bradykinin or ADP. LPC also did not inhibit relaxations produced by SIN 1, an endothelium-derived relaxing factor-nitric oxide donor. After treatment of the rings with pertussis toxin, LPC no longer inhibited the endothelium-dependent relaxations to serotonin. Although LPC inhibited the responses of membrane-bound receptors that activate the pertussis toxin-sensitive Gi protein, LPC did not affect the endothelium-dependent relaxations evoked by direct activation of the pertussis toxin-sensitive Gi protein by fluoride. These results suggest that LPC selectively inhibits a Gi protein-dependent pathway in porcine endothelial cells possibly by disrupting receptor-G protein interactions. LPC that is associated with oxidized LDL may mediate in part the dysfunction in the endothelial Gi protein-dependent pathway associated with hypercholesterolemia.