Acrolein modifies apolipoprotein A-I in the human artery wall.
Carbonyl stress is implicated in accelerated vascular disease, but little is known about the factors that control the reactions of carbonyls with proteins. Acrolein is a reactive carbonyl generated by the oxidation of lipids and amino acids. It also forms during cigarette smoking. We therefore investigated the possibility that acrolein might react with apolipoprotein A-I (apoA-I), the major protein of high-density lipoprotein (HDL), which plays a critical role in mobilizing cholesterol from artery wall macrophages. Tandem mass spectrometric analysis demonstrated that lysine residues were the only amino acids in apoA-I that were modified by acrolein. Immunohistochemical studies with a monoclonal antibody revealed that acrolein adducts colocalized with apoA-I in human atherosclerotic lesions. Moreover, the ability of apoA-I to remove cholesterol from cultured cells was impaired after exposure to acrolein, suggesting that the carbonyl might interfere with apoA-I's normal function of promoting cholesterol efflux from artery wall cells. Our observations suggest that acrolein may interfere with normal HDL cholesterol transport by modifying apoA-I. This structural damage might play a critical role in atherogenesis by impairing cholesterol removal from artery wall cells.
Shao
Baohai
B
Division of Metabolism, Endocrinology and Nutrition, Box 356426, University of Washington, Seattle, WA 98195. heinecke@u.washington.edu.
O'brien
Kevin D
KD
McDonald
Thomas O
TO
Fu
Xiaoyun
X
Oram
John F
JF
Uchida
Koji
K
Heinecke
Jay W
JW
D000171:Acrolein / Q000494:pharmacology*; D000595:Amino Acid Sequence; D016632:Apolipoprotein A-I / Q000187:drug effects / Q000378:metabolism*; D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism; D003324:Coronary Artery Disease / Q000601:surgery; D016027:Heart Transplantation; D006801:Humans; D007668:Kidney; D008239:Lysine / Q000031:analogs & derivatives; D010446:Peptide Fragments / Q000494:pharmacology; D010743:Phospholipids / Q000378:metabolism; D021241:Spectrometry, Mass, Electrospray Ionization; D014162:Transfection
D016632:Apolipoprotein A-I; D010446:Peptide Fragments; D010743:Phospholipids; D000171:Acrolein; D002784:Cholesterol; D008239:Lysine