title: The mechanism of kinetic inhibition of Cu(II)-induced oxidation of low density lipoprotein by lanthanide ions.
abstract: Oral administration of lanthanum chloride (LaCl(3)) was reported to inhibit atherosclerosis in experimental animals, but the mechanism was not clear. In the present work, the effects of La(III) and other lanthanide ions (Ln(III)) on Cu(II)-induced oxidation of isolated low-density lipoprotein (LDL) and the related mechanism were investigated. By monitoring the formation of conjugated dienes (CD), low concentrations of La(III), Gd(III) and Y(III) were found to inhibit Cu(II)-induced LDL oxidation kinetically, as characterized by the prolongation of the lag time, the decrease of the maximal accumulation of CD, and the maximal rate of CD accumulation. Using 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) and alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone (4-POBN) as spin trapping agents, the electron spin resonance (ESR) results showed that La(III) and Gd(III) at low concentrations significantly decreased the level of free radicals, including alkoxyl radical (LO*), alkyl radical (L*), and a transient radical, alkylperoxyl radical (LOO*), generated during LDL oxidation induced by Cu(II). In addition, Fourier-transform infrared spectroscopy (FT-IR) study revealed that La(III) might cause the conformational change and the less aggregation of apolipoprotein B-100 (apoB) in LDL, as demonstrated by the decreasing contents of alpha-helix, intermolecular beta-sheet, unordered structure and beta-turns, and the increasing contents of intramolecular beta-sheet and beta-strands. The inhibitory effect of Ln(III) on Cu(II)-induced LDL oxidation was discussed on the basis of the decreased free radical level and the second structural changes of apoB in LDL.
authors: Department of Chemical Biology, Peking University School of Pharmaceutical Sciences, Beijing 100083, PR China. lh-mei@etang.com
authors: Hongmei
authors: H
authors: Liu
authors: Yi
authors: Y
authors: Cheng
authors: Jingfen
authors: J
authors: Lu
authors: Rongchang
authors: R
authors: Li
authors: Kui
authors: K
authors: Wang