Gugiu Bogdan G, Mesaros Clementina A, Sun Mingjiang, Gu Xiaorong, Crabb John W, Salomon Robert G
Cole Eye Institute and Lerner Research Institute, Cleveland Clinic Foundation, Ohio 44106, USA.
Chem Res Toxicol. 2006 Feb;19(2):262-71. doi: 10.1021/tx050247f.
Oxidized (ox) phospholipids are receiving growing recognition as important messengers in oxidative stress signaling pathways and as endogenous electrophilic toxins that interfere with protein function through covalent modifications. Phosphatidylcholine lipids predominate in low-density lipoproteins (LDL). Our previous studies of oxLDL identified a family of biologically active oxidatively truncated phosphatidylcholines that are also present in atherosclerotic plaques. In contrast, phosphatidylethanolamine (PE) lipids are extraordinarily abundant in retina. Because photoreceptors contain the most highly unsaturated fatty acids found in vertebrate tissues, these membranes are expected to be especially susceptible to oxidative damage. Here, we report that oxidatively truncated ethanolamine phospholipids (oxPEs) are present in retina. As expected, the most abundant oxPEs, succinyl (2.2 +/- 0.8 pmol/retina) and omega-oxobutyryl (1.5 +/- 1.0 pmol/retina) esters of 2-lysophosphatidylethanolamine, are derived from the docosahexaenoyl ester, the most abundant polyunsaturated PE in retina. However, a large amount of the omega-oxononanoyl ester (1.3 +/- 0.6 pmol/retina), derived from linoleyl-PE, is also present even though linoleate is an order of magnitude less abundant than docosahexenoate in retina. There is a notable trend for the presence in retina of greater amounts, relative to the levels of their precursors, of longer chain homologous aldehydes and alkanedioate monoesters. We considered the possibility that this trend results from differences in the proclivities of various polyunsaturated fatty acyl (PUFA)-PEs to generate these homologous products. Therefore, we examined oxidative cleavage of various PUFA-PEs in small unilamellar vesicles. Alkanedioate monoesters are the major stable end products. Particularly notable is the fact that omega-oxononanoyl-PE levels either do not decline or decline less than those of the analogous aldehydes omega-oxobutyryl-PE or omega-oxovaleryl-PE during autoxidation for 33 h. The resistance of omega-oxononanoyl-PE, as compared with omega-oxobutyryl-PE and omega-oxovaleryl-PE, to further oxidation may contribute to the greater amount of this oxPE relative to its precursor, linoleyl-PE, in retina.
氧化（ox）磷脂作为氧化应激信号通路中的重要信使以及通过共价修饰干扰蛋白质功能的内源性亲电毒素，正日益受到关注。磷脂酰胆碱脂质在低密度脂蛋白（LDL）中占主导地位。我们之前对氧化型低密度脂蛋白（oxLDL）的研究鉴定出了一类具有生物活性的氧化截短磷脂酰胆碱，它们也存在于动脉粥样硬化斑块中。相比之下，磷脂酰乙醇胺（PE）脂质在视网膜中极为丰富。由于光感受器含有脊椎动物组织中最高度不饱和的脂肪酸，预计这些膜特别容易受到氧化损伤。在此，我们报告氧化截短的乙醇胺磷脂（oxPEs）存在于视网膜中。正如预期的那样，最丰富的oxPEs，即2 - 溶血磷脂酰乙醇胺的琥珀酰（2.2±0.8 pmol/视网膜）和ω - 氧代丁酰（1.5±1.0 pmol/视网膜）酯，源自二十二碳六烯酰酯，这是视网膜中最丰富的多不饱和PE。然而，大量源自亚油酰 - PE的ω - 氧代壬酰酯（1.3±0.6 pmol/视网膜）也存在，尽管亚油酸在视网膜中的含量比二十二碳六烯酸低一个数量级。相对于其前体水平，视网膜中存在更多长链同源醛和链烷二酸单酯，这一趋势值得注意。我们考虑了这种趋势可能是由于各种多不饱和脂肪酰（PUFA） - PEs生成这些同源产物的倾向不同所致。因此，我们研究了小单层囊泡中各种PUFA - PEs的氧化裂解。链烷二酸单酯是主要的稳定终产物。特别值得注意的是，在33小时的自氧化过程中，ω - 氧代壬酰 - PE的水平要么不下降，要么下降幅度小于类似的醛类ω - 氧代丁酰 - PE或ω - 氧代戊酰 - PE。与ω - 氧代丁酰 - PE和ω - 氧代戊酰 - PE相比，ω - 氧代壬酰 - PE对进一步氧化的抗性可能导致视网膜中这种oxPE相对于其前体亚油酰 - PE的含量更高。
