HOCl-Mediated Glycerophosphocholine and Glycerophosphoethanolamine Generation from Plasmalogens in Phospholipid Mixtures
HOCl-Mediated Glycerophosphocholine and Glycerophosphoethanolamine Generation from Plasmalogens in Phospholipid Mixtures
复制标题
DOI：
10.1007/s11745-009-3365-8
复制
发表时间：
2010-01-01
期刊：
影响因子：
1.9
通讯作者：
Fuchs, Beate
中科院分区：
文献类型：
--
作者：
Lessig, Jacqueline;Fuchs, Beate
许多哺乳动物组织和细胞除了含有(双酰基)磷脂外，还含有相当数量的血浆原，它们可能作为重要的抗氧化剂发挥作用。除了乙烯基醚键的高敏感性所介导的“清道夫”功能外，血浆原的功能目前还不清楚。此外，越来越多的证据表明，纤溶酶原降解产物在炎症过程中具有有害影响。在先前的研究中，甘油磷胆碱(GPC)的形成被证实是次氯酸(HOCl)氧化时一种新的血浆蛋白原降解途径，但这些研究是在简单的模型系统中进行的。在这里，我们在一个更复杂的系统中检测血浆蛋白原的降解，以评估在存在其他高度不饱和的甘油磷脂(GPL)的情况下，GPC的生成是否也是主要途径，这些高度不饱和的甘油磷脂(GPL)代表HOCl靶标的额外反应部位。利用MALDI-TOF质谱仪和P-31核磁共振波谱，我们证实了含有血浆原的GPL混合物在HOCl诱导下降解的第一步是乙烯基醚键的攻击，从而产生1-溶血磷脂酰胆碱(LysoPtdCho)或1-溶血磷脂酰乙醇胺。在第二步中，HOCl与1-lysoPtdCho的sn-2位上的脂肪酰基残基反应。与类似的二酰基-GPL相比，该反应的速度大约快三倍。因此，血浆原生成的GPC和甘油磷乙醇胺(GPE)是在病理条件下HOCl攻击血浆原的乙烯基醚键而形成的相关产物。
Many mammalian tissues and cells contain, in addition to (diacyl) phospholipids, considerable amounts of plasmalogens, which may function as important antioxidants. Apart from the "scavenger" function mediated by the high sensitivity of the vinyl-ether bond, the functional role of plasmalogens is so far widely unknown. Furthermore, there is increasing evidence that plasmalogen degradation products have harmful effects in inflammatory processes. In a previous investigation glycerophosphocholine (GPC) formation was verified as a novel plasmalogen degradation pathway upon oxidation with hypochlorous acid (HOCl), however these investigations were performed in simple model systems. Herein, we examine plasmalogen degradation in a more complex system in order to evaluate if GPC generation is also a major pathway in the presence of other highly unsaturated glycerophospholipids (GPL) representing an additional reaction site of HOCl targets. Using MALDI-TOF mass spectrometry and P-31 NMR spectroscopy, we confirmed that the first step of the HOCl-induced degradation of GPL mixtures containing plasmalogens is the attack of the vinyl-ether bond resulting in the generation of 1-lysophosphatidylcholine (lysoPtdCho) or 1-lysophosphatidylethanolamine. In the second step HOCl reacts with the fatty acyl residue in the sn-2 position of 1-lysoPtdCho. This reaction is about three times faster in comparison to comparable diacyl-GPL. Thus, the generation of GPC and glycerophosphoethanolamine (GPE) from plasmalogens are relevant products formed from HOCl attack on the vinyl-ether bond of plasmalogens under pathological conditions.