Copper and cell‐oxidized low‐density lipoprotein induces activator protein 1 in fibroblasts, endothelial and smooth muscle cells

FEBS Letters

Frey-Fressart, Véronique¹  Djavaheri-Mergny, Mojgan²  Delattre, Jacques¹  Mazière, Cécile³  Mazière, Jean-Claude³ 

[1] Laboratoire de Biochimie, Hôpital de la Salpêtrière, 47 Bd de l'Hôpital, 75651 Paris Cedex 06, France;Laboratoire de Dermatologie, INSERM U312, Hôpital Saint-Louis, 1 Av. Claude Vellefaux, 75475 Paris, France;Laboratoire de Biochimie, CHU d'Amiens, Hôpital Nord, Place Victor Pauchet, 80054 Amiens Cedex 01, France

关键词: Oxidized LDL;    Oxidative stress;    AP1;    Fibroblasts;    Endothelial cells;    Smooth muscle cells;    Atherosclerosis;    c-LDL;    control low-density lipoprotein;    Cu-LDL;    Cu2+-oxidized LDL;    E-LDL;    endothelial cell-oxidized LDL;    TBARS;    thiobarbituric-acid-reactive substances (lipid peroxidation end-products);   

DOI  :  10.1016/S0014-5793(97)00545-0

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The effect of cupric ion- or endothelial cell-oxidized low-density lipoproteins (LDL) on transcription factor AP1 activation was investigated by electrophoretic mobility shift assay. Both oxidized LDL induced AP1 activation in fibroblasts, endothelial and smooth muscle cells. This phenomenon was also observed in the presence of cycloheximide. α-Tocopherol, a lipophilic free radical scavenger, and N-acetylcysteine, an hydrophilic antioxidant, partially inhibited the stimulatory effect of Cu²⁺-oxidized LDL. LDL modified by the mixture of the oxygen radicals OH· and O₂·⁻, which generated lipid peroxidation products, also 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 activation mechanism. Since AP1 activity is essential for the regulation of genes involved in cell growth and differentiation, our study suggests that the oxidative stress induced by oxidized LDL might be related to the fibroproliferative response observed in the atherosclerotic plaque.

【 授权许可】

Unknown