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Can J Physiol Pharmacol. 2006 Jan;84(1):141-7.

Folic acid inhibits homocysteine-induced superoxide anion production and nuclear factor kappa B activation in macrophages.

Author information

1
Department of Animal Science, University of Manitoba, National Centre for Agri-Food Research in Medicine, Laboratory of Integrative Biology, NCARM, St Boniface Hospital Research Centre, Winnipeg, Canada.

Abstract

Folic acid supplementation is a promising approach for patients with cardiovascular diseases associated with hyperhomocysteinemia. We have demonstrated that homocysteine (Hcy) activates nuclear factor-kappaB (NF-kappaB), 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-kappaB activation in macrophages. Hcy treatment (100 micromol/L) resulted in NF-kappaB activation and increased monocyte chemoattractant protein-1 (MCP-1) expression in THP-1 derived macrophages. Hcy-induced NF-kappaB 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 p47phox 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 p47phox subunit. Consequently, Hcy-induced NF-kappaB 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.

PMID:
16845898
DOI:
10.1139/Y05-136
[Indexed for MEDLINE]

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