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Browsing University of Manitoba Scholarship (login required) by Author "Au-Yeung, KKW"
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- ItemRestrictedFolic acid inhibits homocysteine-induced superoxide anion production and nuclear factor kappa B activation in macrophages(2006-01-31) Au-Yeung, KKW; Yip, JCW; Siow, YL; O, KFolic 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.