Vitamin C protects low-density lipoprotein from homocysteine-mediated oxidation.
Homocysteine, an atherogenic amino acid, promotes iron-dependent oxidation of low-density lipoprotein (LDL). We investigated whether vitamin C, a physiological antioxidant, could protect LDL from homocysteine-mediated oxidation. LDL (0.2 mg of protein/ml) was incubated at 37 degrees C with homocysteine (1000 microM) and ferric iron (10-100 microM) in either the absence (control) or presence of vitamin C (5-250 microM). Under these conditions, vitamin C protected LDL from oxidation as evidenced by an increased lag time preceding lipid diene formation (> or = 5 vs. 2.5 h for control), decreased thiobarbituric acid-reactive substances accumulation (< or = 19 +/- 1 nmol/mg when vitamin C > or = 10 microM vs. 32 +/- 3 nmol/mg for control, p <.01), and decreased lipoprotein anodic electrophoretic mobility. Near-maximal protection was observed at vitamin C concentrations similar to those in human blood (50-100 microM); also, some protection was observed even at low concentrations (5-10 microM). This effect resulted neither from altered iron redox chemistry nor enhanced recycling of vitamin E in LDL. Instead, similar to previous reports for copper-dependent LDL oxidation, we found that vitamin C protected LDL from homocysteine-mediated oxidation through covalent lipoprotein modification involving dehydroascorbic acid. Protection of LDL from homocysteine-mediated oxidation by vitamin C may have implications for the prevention of cardiovascular disease.
Alul
Rushdi H
RH
Chicago College of Osteopathic Medicine, Midwestern University, Downers Grove, IL 60515, USA.
Wood
Michael
M
Longo
Joseph
J
Marcotte
Anthony L
AL
Campione
Allan L
AL
Moore
Michael K
MK
Lynch
Sean M
SM
D001205:Ascorbic Acid / Q000378:metabolism / Q000494:pharmacology*; D002318:Cardiovascular Diseases / Q000378:metabolism; D003300:Copper / Q000378:metabolism; D003683:Dehydroascorbic Acid / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005609:Free Radicals; D006710:Homocysteine / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007501:Iron / Q000378:metabolism; D008074:Lipoproteins / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism*; D016877:Oxidants / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010100:Oxygen / Q000378:metabolism*; D013696:Temperature; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D013997:Time Factors; D014810:Vitamin E / Q000378:metabolism
D005609:Free Radicals; D008074:Lipoproteins; D008077:Lipoproteins, LDL; D016877:Oxidants; D017392:Thiobarbituric Acid Reactive Substances; D006710:Homocysteine; D014810:Vitamin E; D003300:Copper; D007501:Iron; D001205:Ascorbic Acid; D010100:Oxygen; D003683:Dehydroascorbic Acid