Phosphatidylethanolamine oxidation products

FIGURE 8.1 Oxidation products formed from phosphatidylethanolamine (PLPE) lipid, including low-molecular weight aldehydes, oxygen addition, and oxidative cleavage produets of PLPE, corresponding DAG and lysoPE forms. 

Schiff base compounds formed by the interaction of oxidation products with proteins, phospholipids and nucleic acids produce chromophores showing characteristic fluorescence spectra. The Schiff base formed between malonaldehyde and amino acids is attributed to the conjugated structure -NH=CH-CH=CH-NH-. Lipid-soluble fluorescence chromophores are produced from oxidized phospholipids and from oxidized fatty acid esters in the presence of phospholipids. These chromophores have fluorescence emission maxima at 435-440 nm and excitation maxima at 365 nm. The Schiff base of malonaldehyde and phospholipids has a higher wavelength maximum for emission (475 nm) and excitation (400 nm). The interaction between oxidized arachidonic acid and dipalmityl phosphatidylethanolamine produce similar fluorescence spectra (maximum excitation at 360-90 nm and maximum emission at 430-460 nm). The products from oxidized arachidonic acid and DNA have characteristic fluorescence spectra, with excitation maximum at 315 nm and emission maximum at 325 nm. Similar fluorescence spectra, with excitation maximum at 320 mn and emission maximum at420 nm, are obtained from the interactions of either lipid hydroperoxides or secondary oxidation products with DNA in the presence of metals and reducing agents, or different aldehydes, ketones and dimeric compounds from oxidized linolenate. Therefore, the Schiff base produced from various oxidized lipids and phospholipids and DNA may be considered to be due to a mixture of closely related chromophores. 

The synergism exhibited by the ternary mixture of a-tocopherol, ascorbic acid and phospholipids has been shown to be due to the stabilization of a-tocopherol, on the basis of ESR studies with methyl linolenate oxidized at 90°C to detect the free radicals of a-tocopherol and ascorbic acid. Evidence was obtained by this technique for the formation of nitroxide radicals (R-N-0 ) in the presence of phosphatidylserine or phosphatidylethanolamine or soybean lecithin and oxidized methyl linolenate. However, as pointed out earlier (Section C), the synergistic activity of this ternary mixture may be derived from antioxidant products formed from the phospholipids at elevated temperatures by the Maillard browning reaction (Chapter 11). 

Prolonged inhalation of dusts by humans (156), rodents (157,158), and other species (159,160) is associated with an increase in the number of type II cells and increased secretion of surfactant. The stimulation of surfactant appears to be directly related to the toxicity of the dust. It may be so florid, as in acute silicosis, that flooding of the alveolar spaces with surfactant lipids and associated proteins may occur, a condition known as alveolar lipoproteinosis (156). In experimental lipoproteinosis in the rat, the major lipid component is disaturated phosphatidylcholine (157), but all lipid fractions are increased. In the sheep model of experimental silicosis, phosphatidylglycerol, phosphatidylethanolamine, and phosphatidylinositol, showed the greatest increases following silica exposure (159). The excess production of surfactant in response to silica dust may be an adaptive response, perhaps to reduce particle cytotoxicity or to compensate for oxidant-induced lipid peroxidation (147,161). 

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