Folic acid inhibits homocysteine-induced superoxide anion production and nuclear factor kappa B activation in macrophagesThis paper is one of a selection of papers published in this Special Issue, entitled Young Investigator's Forum
| Autor: | Kathy K.W. Au-Yeung, Karmin O, Johnny C W Yip, Yaw L. Siow |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Pharmacology
medicine.medical_specialty Hyperhomocysteinemia NADPH oxidase Homocysteine biology Physiology Superoxide Monocyte NF-κB General Medicine medicine.disease NFKB1 medicine.disease_cause chemistry.chemical_compound medicine.anatomical_structure Endocrinology chemistry Physiology (medical) Internal medicine medicine biology.protein Oxidative stress |
| Zdroj: | Canadian Journal of Physiology and Pharmacology. 84:141-147 |
| ISSN: | 1205-7541 0008-4212 |
| DOI: | 10.1139/y05-136 |
| Popis: | Folic acid supplementation is a promising approach for patients with cardiovascular diseases associated with hyperhomocysteinemia. We have demonstrated that homocysteine (Hcy) activates nuclear factor-κB (NF-κB), 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-κB activation in macrophages. Hcy treatment (100 μmol/L) resulted in NF-κB activation and increased monocyte chemoattractant protein-1 (MCP-1) expression in THP-1 derived macrophages. Hcy-induced NF-κB 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-κB 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|