Identification of Oxidatively Truncated Ethanolamine Phospholipids in Retina and Their Generation from Polyunsaturated Phosphatidylethanolamines

• Published in: Chemical research in toxicology 2006-02, Vol.19 (2), p.262-271
• Main Authors: Gugiu, Bogdan G, Mesaros, Clementina A, Sun, Mingjiang, Gu, Xiaorong, Crabb, John W, Salomon, Robert G
• Format: Article
• Language: English
• Subjects: Animals; Ethanolamine - chemistry; Ethanolamine - metabolism; In Vitro Techniques; Molecular Structure; Oxidation-Reduction; Phosphatidylethanolamines - chemistry; Phosphatidylethanolamines - metabolism; Phospholipids - biosynthesis; Phospholipids - chemistry; Phospholipids - metabolism; Rats; Retina - chemistry; Retina - metabolism; Time Factors
• ISSN: 0893-228X; 1520-5010
• 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 ω-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 ω-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 ω-oxononanoyl-PE levels either do not decline or decline less than those of the analogous aldehydes ω-oxobutyryl-PE or ω-oxovaleryl-PE during autoxidation for 33 h. The resistance of ω-oxononanoyl-PE, as compared with ω-oxobutyryl-PE and ω-oxovaleryl-PE, to further oxidation may contribute to the greater amount of this oxPE relative to its precursor, linoleyl-PE, in retina.