TY - JOUR

T1 - Evidence for roles of radicals in protein oxidation in advanced human atherosclerotic plaque

AU - Fu, S

AU - Davies, Michael Jonathan

AU - Stocker, R

AU - Dean, R T

PY - 1998/8/1

Y1 - 1998/8/1

N2 - Oxidative damage might be important in atherogenesis. Oxidized lipids are present at significant concentrations in advanced human plaque, although tissue antioxidants are mostly present at normal concentrations. Indirect evidence of protein modification (notably derivatization of lysine) or oxidation has been obtained by immunochemical methods; the specificities of these antibodies are unclear. Here we present chemical determinations of six protein-bound oxidation products: dopa, o-tyrosine, m-tyrosine, dityrosine, hydroxyleucine and hydroxyvaline, some of which reflect particularly oxy-radical-mediated reaction pathways, which seem to involve mainly the participation of transition- metal ions. We compared the relative abundance of these oxidation products in normal intima, and in human carotid plaque samples with that observed after radiolytically generated hydroxyl radical attack on BSA in vitro. The close similarities in relative abundances in the latter two circumstances indicate that hydroxyl radical damage might occur in plaque. The relatively higher level of dityrosine in plaque than that observed after radiolysis suggests the additional involvement of HOCl-mediated reactions in advanced plaque.

AB - Oxidative damage might be important in atherogenesis. Oxidized lipids are present at significant concentrations in advanced human plaque, although tissue antioxidants are mostly present at normal concentrations. Indirect evidence of protein modification (notably derivatization of lysine) or oxidation has been obtained by immunochemical methods; the specificities of these antibodies are unclear. Here we present chemical determinations of six protein-bound oxidation products: dopa, o-tyrosine, m-tyrosine, dityrosine, hydroxyleucine and hydroxyvaline, some of which reflect particularly oxy-radical-mediated reaction pathways, which seem to involve mainly the participation of transition- metal ions. We compared the relative abundance of these oxidation products in normal intima, and in human carotid plaque samples with that observed after radiolytically generated hydroxyl radical attack on BSA in vitro. The close similarities in relative abundances in the latter two circumstances indicate that hydroxyl radical damage might occur in plaque. The relatively higher level of dityrosine in plaque than that observed after radiolysis suggests the additional involvement of HOCl-mediated reactions in advanced plaque.

KW - Adult

KW - Amino Acids

KW - Arteriosclerosis

KW - Blood Proteins

KW - Dihydroxyphenylalanine

KW - Female

KW - Humans

KW - Hydroxides

KW - Hydroxyl Radical

KW - Hypochlorous Acid

KW - Male

KW - Middle Aged

KW - Oxidation-Reduction

KW - Peroxides

KW - Proteins

KW - Serum Albumin, Bovine

KW - Tunica Intima

M3 - Journal article

C2 - 9677308

VL - 333 ( Pt 3)

SP - 519

EP - 525

JO - Biochemical Journal

JF - Biochemical Journal

SN - 0264-6021

ER -