Induction of glutathione synthesis by oxidized low-density lipoprotein and 1-palmitoyl-2-arachidonyl phosphatidylcholine: protection against quinone-mediated oxidative stress.
Induction of glutathione synthesis by oxidized low-density lipoprotein and 1-palmitoyl-2-arachidonyl phosphatidylcholine: protection against quinone-mediated oxidative stress.
复制标题
氧化低密度脂蛋白和 1-棕榈酰-2-花生四烯酰磷脂酰胆碱诱导谷胱甘肽合成：防止醌介导的氧化应激。
DOI：
10.1042/0264-6021:3620051
复制
发表时间：
2002
期刊：
影响因子：
--
通讯作者：
Darley-Usmar,VictorM
中科院分区：
文献类型：
--
作者：
Moellering,DouglasR;Levonen,Anna-Liisa;Go,Young-Mi;Patel,RakeshP;Dickinson,DaleA;Forman,HenryJay;Darley-Usmar,VictorM
内皮细胞暴露于氧化低密度脂蛋白（oxLDL）导致不同的细胞效应，包括诱导细胞内抗氧化剂GSH。目前尚不清楚脂质或蛋白质衍生的氧化产物是否会引起GSH诱导，以及这是否涉及其合成中关键酶谷氨酸-半胱氨酸连接酶（GCL）的活性增加。此外，oxLDL暴露对细胞抗氧化应激能力的影响以前尚未研究过。在本研究中，我们发现，在牛主动脉内皮细胞，LDL或1-棕榈酰-2-花生四烯酸磷脂酰胆碱氧化不同的活性氧和氮物种诱导GSH的合成。然而，在暴露于oxLDL期间阻止GSH合成引起广泛的细胞死亡。介导GSH诱导被证明是一种极性脂质，并导致GCL的活性增加以及GCL的调节亚基的蛋白水平增加。预处理与氧化低密度脂蛋白和氧化低密度脂蛋白的极性脂质亚组分保护细胞对2，3-二甲氧基萘醌（DMNQ），超氧化物和H2 O2形成的化合物的毒性。低水平的脂质过氧化产物启动细胞保护途径的潜力进行了讨论。
Exposure of endothelial cells to oxidized low-density lipoprotein (oxLDL) leads to diverse cellular effects, including induction of the intracellular antioxidant GSH. It is not known whether lipid-or protein-derived oxidation products cause GSH induction and whether this involves increased activity of the key enzyme in its synthesis, glutamate—cysteine ligase (GCL). Furthermore, the effect of oxLDL exposure on the cell's ability to combat oxidative stress has not been previously examined. In the present study we found that, in bovine aortic endothelial cells, LDL or 1-palmitoyl-2-arachidonyl phosphatidylcholine oxidized by different reactive oxygen and nitrogen species induced GSH synthesis. However, prevention of GSH synthesis during exposure to oxLDL caused extensive cell death. The mediator causing GSH induction was shown to be a polar lipid and resulted in the increased activity of GCL as well as increased protein levels of the regulatory subunit of GCL. Pretreatment with both oxLDL and the polar lipid subfraction of the oxLDL protected cells against the toxicity of 2,3-dimethoxynaphthoquinone (DMNQ), a superoxide- and H2O2-forming compound. The potential of a low level of lipid peroxidation products to initiate cytoprotective pathways are discussed.