TY - JOUR
T1 - Structural characterization and immunochemical detection of a fluorophore derived from 4-hydroxy-2-nonenal and lysine
AU - Tsai, Lin
AU - Szweda, Pamela A.
AU - Vinogradova, Olga
AU - Szweda, Luke I.
PY - 1998/7/7
Y1 - 1998/7/7
N2 - Aging and the progression of certain degenerative diseases are accompanied by increases in intracellular fluorescent material, termed 'lipofuscin' and ceroid, respectively. These pigments are observed within granules composed, in part, of damaged protein and lipid. Modification of various biomolecules by aldehyde products of lipid peroxidation is believed to contribute to lipofuscin and ceroid formation. However, little direct evidence currently exists because the structures responsible for the fluorescent, cross-linked nature of this material are not well characterized. In this study, we have identified a fluorescent product formed in the reaction of N(α)-acetyllysine and 4-hydroxy-2-nonenal (HNE), a major product of lipid peroxidation and the most reactive of these compounds under physiological conditions [Esterbauer, H., Shaur, R. J. and Zollner, H. (1991) Free Radical Biol. Med. 11, 81-128]. This fluorescent compound, characterized as a 2-hydroxy-3-imino-1,2-dihydropyrrol derivative, appears to form upon oxidative cyclization of the nonfluorescent 2:1 lysine-HNE Michael adduct- Schiff base cross-link. Polyclonal antibody was raised to the Nα- acetyllysine-HNE fluorophore and found to be highly specific to the chromophore structure of the compound. This antibody has been used to conclusively demonstrate that the lysine-HNE derivative of this fluorophore forms on protein upon exposure to HNE. The results of this study therefore provide the basis for future investigations on the contribution(s) of HNE- derived fluorophore formation to lipofuscin and ceroid accumulation.
AB - Aging and the progression of certain degenerative diseases are accompanied by increases in intracellular fluorescent material, termed 'lipofuscin' and ceroid, respectively. These pigments are observed within granules composed, in part, of damaged protein and lipid. Modification of various biomolecules by aldehyde products of lipid peroxidation is believed to contribute to lipofuscin and ceroid formation. However, little direct evidence currently exists because the structures responsible for the fluorescent, cross-linked nature of this material are not well characterized. In this study, we have identified a fluorescent product formed in the reaction of N(α)-acetyllysine and 4-hydroxy-2-nonenal (HNE), a major product of lipid peroxidation and the most reactive of these compounds under physiological conditions [Esterbauer, H., Shaur, R. J. and Zollner, H. (1991) Free Radical Biol. Med. 11, 81-128]. This fluorescent compound, characterized as a 2-hydroxy-3-imino-1,2-dihydropyrrol derivative, appears to form upon oxidative cyclization of the nonfluorescent 2:1 lysine-HNE Michael adduct- Schiff base cross-link. Polyclonal antibody was raised to the Nα- acetyllysine-HNE fluorophore and found to be highly specific to the chromophore structure of the compound. This antibody has been used to conclusively demonstrate that the lysine-HNE derivative of this fluorophore forms on protein upon exposure to HNE. The results of this study therefore provide the basis for future investigations on the contribution(s) of HNE- derived fluorophore formation to lipofuscin and ceroid accumulation.
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U2 - 10.1073/pnas.95.14.7975
DO - 10.1073/pnas.95.14.7975
M3 - Article
C2 - 9653125
AN - SCOPUS:0032493431
SN - 0027-8424
VL - 95
SP - 7975
EP - 7980
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 14
ER -