COPPER AND CELL-OXIDIZED LOW-DENSITY-LIPOPROTEIN INDUCES ACTIVATOR PROTEIN-1 IN FIBROBLASTS, ENDOTHELIAL AND SMOOTH-MUSCLE CELLS

The effect of cupric ion- or endothelial cell-oxidized low-density lip oproteins (LDL) on transcription factor AP1 activation was investigate d by electrophoretic mobility shift assay, Both oxidized LDL induced A P1 activation in fibroblasts, endothelial and smooth muscle cells, Thi s phenomenon was also observed in the presence of cycloheximide, alpha -Tocopherol, a lipophilic free radical scavenger, and N-acetylcysteine , an hydrophilic antioxidant, partially inhibited the stimulatory effe ct of Cu2+-oxidized LDL. LDL modified by the mixture of the oxygen rad icals OH . and O2(.-), which generated lipid peroxidation products, al so initiated AP1 activation, whereas LDL modified by OH . alone, which did not lead to marked LDL lipid peroxidation, was ineffective, Thus, lipid peroxidation products seem at least partially involved in the a ctivation mechanism, Since AP1 activity is essential for the regulatio n of genes involved in cell growth and differentiation, our study sugg ests that the oxidative stress induced by oxidized LDL might he relate d to the fibroproliferative response observed in the atherosclerotic p laque. (C) 1997 Federation of European Biochemical Societies.