2. Zhang WJ

Frie B

0

Endothelial activation and monocyte adhesion are initiating steps in atherogenesis thought to be caused in part by oxidative stress. The metabolic thiol antioxidant α-lipoic acid has been suggested to be of therapeutic value in pathologies associated with redox imbalances. We investigated the role of (R)-α-lipoic acid (LA) vs. glutathione and ascorbic acid in tumor necrosis factor α (TNF-α) -induced adhesion molecule expression and nuclear factor κB (NF-κB) signaling in human aortic endothelial cells (HAEC). Preincubation of HAEC for 48 h with LA (0.05–1 mmol/l) dose-dependently inhibited TNF-α (10 U/ml) -induced adhesion of human monocytic THP-1 cells, as well as mRNA and protein expression of E-selectin, vascular cell adhesion molecule 1 and intercellular adhesion molecule 1. LA also strongly inhibited TNF-α-induced mRNA expression of monocyte chemoattractant protein-1 but did not affect expression of TNF-α receptor 1. Furthermore, LA dose-dependently inhibited TNF-α-induced IκB kinase activation, subsequent degradation of IκB, the cytoplasmic NF-κB inhibitor, and nuclear translocation of NF-κB. In contrast, TNF-α-induced NF-κB activation and adhesion molecule expression were not affected by ascorbic acid or by manipulating cellular glutathione status with l-2-oxo-4-thiazolidinecarboxylic acid, N-acetyl-l-cysteine, or d,l-buthionine-S,R-sulfoximine. Our data show that clinically relevant concentrations of LA, but neither vitamin C nor glutathione, inhibit adhesion molecule expression in HAEC and monocyte adhesion by inhibiting the IκB/NF-κB signaling pathway at the level, or upstream, of IκB kinase.—Zhang, W.-J., Frei, B. α-Lipoic acid inhibits TNF-α-induced NF-κB activation and adhesion molecule expression in human aortic endothelial cells.

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The FASEB Journal

vol. 15 no. 13 2423-2432

2001

http://www.fasebj.org/content/15/13/2423.short