MODIFICATION OF ε‐AMINO GROUP OF LYSINES, CHOLESTEROL OXIDATION AND OXIDIZED LIPID‐APOPROTEIN CROSS‐LINK FORMATION BY PORPHYRIN‐PHOTOSENSITIZED OXIDATION OF HUMAN LOW DENSITY LIPOPROTEINS

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Abstract
Abstract—When incorporated into LDL, protoporphyrin and the porphyrin mixture constituting the trade mark Photofrin II photosensitize peroxidations of cholesterol and lipids. Not only 5a‐hydroperoxicholesterol, the specific product of cholesterol oxidation by1O2but also the epimeric 6‐hydroperoxicholesterols are produced as shown by HPLC. In addition to malonaldehyde‐like substances, the formation of 4‐hydroxynonenal, a highly reactive and toxic aldehyde resulting from lipid peroxide breakdown is detected. These products are also formed by dark radical chain reactions of lipid photoperoxides induced by photosensitization. The involvement of lipid photoperoxidation in LDL apoprotein modification is demonstrated by following the derivatization of e‐NH2groups of Lys residues which are necessary to binding to the LDL receptor. As a result, photosensitized LDL cannot bind to their receptors on fibroblasts. Lys residues are not sensitive to direct photodynamic reaction as confirmed by delipidation of LDL and solubilization of apoLDL in 1% SDS which totally inhibit Lys derivatization without affecting the degradation of Trp residues susceptible to the photodynamic attack. Another consequence of lipid peroxidation at the protein level is the formation of cross‐links between apoLDL and photooxidized lipids as shown using LDL loaded with radioactive arachidonic acid. On the other hand, cholesterol photoperoxidation does not lead to protein‐oxidized cholesterol cross‐links. These reactions between peroxidized lipids and LDL proteins are also responsible for the formation of lipofuscin‐like fluorescent pigments encountered in all aging processes. The biological and biomedical consequences of these results are discussed.

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