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

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dc.contributor.authorAu-Yeung, KKW
dc.contributor.authorYip, JCW
dc.contributor.authorSiow, YL
dc.contributor.authorO, K
dc.date.accessioned2007-10-09T19:00:18Z
dc.date.available2007-10-09T19:00:18Z
dc.date.issued2006-01-31
dc.description.abstractFolic 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.en
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dc.identifier.citation0008-4212; CAN J PHYSIOL PHARMACOL, JAN 2006, vol. 84, no. 1, p.141 to 147.en
dc.identifier.doihttp://dx.doi.org/10.1139/Y05-136
dc.identifier.urihttp://hdl.handle.net/1993/2918
dc.language.isoengen_US
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dc.rightsopen accessen_US
dc.statusPeer revieweden
dc.subjecthomocysteineen
dc.subjectfolic aciden
dc.subjectoxidative stressen
dc.subjectNADPH oxidaseen
dc.subjectNF-kappa Ben
dc.subjectCHEMOATTRACTANT PROTEIN-1 EXPRESSIONen
dc.subjectCORONARY-ARTERY DISEASEen
dc.subjectENDOTHELIAL DYSFUNCTIONen
dc.subjectNADPH-OXIDASEen
dc.subjectSMOOTH-MUSCLEen
dc.subjectPLASMA HOMOCYSTEINEen
dc.subjectOXIDATIVE STRESSen
dc.subjectVASCULAR-DISEASEen
dc.subjectHYPERHOMOCYSTEINEMIAen
dc.titleFolic acid inhibits homocysteine-induced superoxide anion production and nuclear factor kappa B activation in macrophagesen
dc.typejournal articleen_US
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