Folic acid inhibits homocysteine-induced superoxide anion production and nuclear factor kappa B activation in macrophages
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Date
2006-01-31
Authors
Au-Yeung, KKW
Yip, JCW
Siow, YL
O, K
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Abstract
Folic acid supplementation is a promising approach for patients with cardiovascular diseases associated with hyperhomocysteinerma. We have demonstrated that homocysteine (Hey) activates nuclear factor-kappa B (NF-kappa B), a transcription factor that plays an important role in inflammatory responses. The aim of the present Study was to investigate the effect of folic acid on Hcy-induced NF-kappa B activation in macrophages. Hey treatment (100 mu mol/L) resulted in NF-kappa B activation and increased monocyte chemoattractant protein-1 (MCP-1) expression in THP-1 derived macrophages. Hcy-induced NF-kappa B activation was associated with a significant increase in the intracellular Superoxide anion levels. There was a significant increase in phosphorylation and membrane translocation of NADPH oxidase p47(phox) subunit in Hcy-treated cells. Addition of folic acid (200 ng/mL) to the culture medium abolished NADPH oxidase-dependent Superoxide anion generation in macrophages by preventing phosphorylation of: p47(phox) subunit. Consequently, Hcy-induced NF-kappa B activation and MCP-1 expression was inhibited. Such an inhibitory effect of folic acid was independent of its Hcy-lowering ability. Taken together, these results suggest that folic acid treatment can effectively inhibit Hcy-induced oxidative stress and inflammatory responses in macrophages. This may represent one of the mechanisms by which folic acid supplementation exerts a protective effect in cardiovascular disorders.
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Keywords
homocysteine, folic acid, oxidative stress, NADPH oxidase, NF-kappa B, CHEMOATTRACTANT PROTEIN-1 EXPRESSION, CORONARY-ARTERY DISEASE, ENDOTHELIAL DYSFUNCTION, NADPH-OXIDASE, SMOOTH-MUSCLE, PLASMA HOMOCYSTEINE, OXIDATIVE STRESS, VASCULAR-DISEASE, HYPERHOMOCYSTEINEMIA
Citation
0008-4212; CAN J PHYSIOL PHARMACOL, JAN 2006, vol. 84, no. 1, p.141 to 147.