Fluorescent and cross-linked proteins formed by free radical and aldehyde species generated during lipid oxidation.

One of the mechanisms for the formation of lipofuscin-like fluorescent substances is considered to be related to lipid oxidation of tissues. Induction of lipid oxidation in tissues or cells produces cross-links and borohydride-reducible functions together with fluorescence in proteins. In order to elucidate the structures of fluorophores, cross-links and borohydride-reducible functions produced in proteins by lipid oxidation, the reactions of a lipid peroxy free radical with amino acids and proteins, and those of an aldehyde with primary amines were investigated. We demonstrated here two possible types of the reactions that produce the modified proteins. A peroxy free radical generated during lipid oxidation may attack the tyrosine residue in proteins to form the tyrosine radical which may be in turn dimerized into fluorescent and cross-linked tyrosine dimer. aldehyde species formed by degradation of the peroxy free radical may be polymerized into dimer, trimer, tetramer and so on, which may react with the amino groups of protein to produce fluorescence, cross-links and borohydride-reducible functions. Cross-links can be produced by the formation of Schiff base between the tetrameric dialdehyde and the amino groups of proteins.