Submitted to: Photochemistry and Photobiology
Publication Type: Peer reviewed journal
Publication Acceptance Date: 10/20/2003
Publication Date: 1/20/2004
Citation: Chowdhury, P.K., Halder, M., Choudhury, P.K., Kraus, G. A., Desai, M.J., Armstrong, D.W. Casey, T.A., Rasmussen, M.A., Petrich, J.W. 2004. Generation of fluorescent adducts of malondialdehyde and amino acids: towards an understanding of lipofuscin. Photochemistry and Photobiology. 79:21-25. Interpretive Summary: Lipofuscin is a yellow-brown, highly fluorescent material that accumulates in slowly dividing animal cells like those in the central nervous system. Lipofuscin is a complex of proteins, lipids, and nucleic acids. It has been implicated in several animal and human diseases, including the prion diseases like scrapie. The fluorescent properties of this material make it useful for the detection of tissue from the central nervous system in meat and also in the diagnosis of prion-type diseases. We have chemically synthesized simple lipofuscin material in the laboratory in order to study its chemical and physical properties. This material was fluorescent and emitted at a broad range of wavelengths, including the orange region of the spectrum.
Technical Abstract: Lipofuscin is a yellow-brown, highly fluorescent pigment that undergoes an age-related progressive accumulation in animal cells, mainly in postmitotic cells. It is a heterogeneous, high-molecular weight material associated with proteins, lipids, and nucleic acids. Lipofuscin is implicated in many aspects of human health, including aging, oxidative stress, macular degeneration, lipid peroxidation, atherosclerosis, dementia (Alzheimer's Disease), and diseases associated with prions. Although the fluorescent properties of lipofuscins have long been recognized, neither histologists nor chemists have yet isolated with pigments themselves or characterized their optical properties. We have prepared and characterized lipofuscin-like species by reacting malondialdehyde (MDA) with cysteine and tryptophan. It is proposed that 3:2 and 2:2 MDA:Cys adducts are formed. A cyclic 1:1 MDA:Trp adduct is also proposed. Whereas previous attempts to synthesize lipofuscin-like species resulted in compounds that were either nonfluorescent or that emitted principally in the blue, the MDA-Cys and MDA-Trp adducts reported here are not only fluorescent, but emit over a broader range, most notably into the orange region of the spectrum, more like naturally occurring lipofuscin.