Aldehydes in cigarette smoke react with the lipid peroxidation product malonaldehyde to form fluorescent protein adducts on lysines.
Cigarette smoke is a risk factor for the development of several diseases, but the exact mechanism responsible has not been well-characterized. Because modification, or adducting, of biomolecules is thought to mediate the toxic effects observed from exposure to a wide variety of harmful chemicals, this study investigated the ability of cigarette smoke to produce specific adducts on a peptide to gain insight into the likely effect on cellular proteins. We describe the modification of the epsilon-amino group of lysine contained in a test peptide with stable fluorescent adducts derived from monofunctional aldehydes occurring in cigarette smoke and malonaldehyde, a product of lipid peroxidation. Utilizing high-performance liquid chromatography, fluorescent measurements, and matrix-assisted laser desorption/ionization time-of-flight mass spectroscopy, the 1,4-dihydropyridine-3,5-dicarbaldehyde and 4-methyl-1,4-dihydropyridine-3,5-dicarbaldehyde derivatives of lysine were identified as products of exposure to cigarette smoke extract and malonaldehyde. These data suggest that cigarette smoke may promote the modification of proteins, like those associated with oxidized low-density lipoprotein, and may contribute to smoking-related disease.
Freeman
Thomas L
TL
Department of Internal Medicine, University of Nebraska Medical Center, Omaha, Nebraska 68198, USA. tlfreeman@unmc.edu
Haver
Alvin
A
Duryee
Michael J
MJ
Tuma
Dean J
DJ
Klassen
Lynell W
LW
Hamel
Frederick G
FG
White
Ronda L
RL
Rennard
Stephen I
SI
Thiele
Geoffrey M
GM
D000447:Aldehydes / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D004095:Dihydropyridines / Q000302:isolation & purification; D005453:Fluorescence; D015227:Lipid Peroxidation; D008239:Lysine / Q000378:metabolism*; D008315:Malondialdehyde / Q000737:chemistry* / Q000378:metabolism; D011506:Proteins / Q000737:chemistry / Q000378:metabolism; D012907:Smoking / Q000009:adverse effects; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013997:Time Factors; D014026:Nicotiana / Q000737:chemistry / Q000633:toxicity*; D014028:Tobacco Smoke Pollution
D000447:Aldehydes; D004095:Dihydropyridines; D011506:Proteins; D014028:Tobacco Smoke Pollution; D008315:Malondialdehyde; D008239:Lysine