Premium
Regulatory effects of curcumin on FOXO3a in human THP‐1 monocytes/macrophages
Author(s) -
Zingg JeanMarc,
Hasan Syeda T,
Azzi Angelo,
Meydani Mohsen
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.95.1
Subject(s) - curcumin , oxidative stress , cd36 , chemistry , inflammation , transcription factor , antioxidant , keap1 , pharmacology , microbiology and biotechnology , biochemistry , biology , gene , immunology
An increased risk for atherosclerosis in the elderly is associated with inflammation and increased oxidative‐ and lipid‐mediated stress in the vascular system. At the molecular level, aging is associated with decreased activity of FOXO3a, a transcription factor centrally involved in regulating several stress resistance and lipid transport genes. Recent evidence has suggested potential benefits from phytochemicals and micronutrients in protecting against oxidative and lipid‐mediated damage, but the molecular mechanisms of these actions are still unclear. Here we investigated whether the dietary polyphenol curcumin can modulate the expression and activity of FOXO3a in THP‐1 cells. Curcumin induced FOXO3a phosphorylation, FOXO3a nuclear translocation, and increased FOXO3a‐mediated gene expression by 2‐fold, as measured using a FOXO3a‐luciferase reporter gene. The curcumin derivative, tetrahydrocurcumin, which has a similar chemical antioxidant activity as curcumin, did not show any measurable effect. Curcumin also influenced the expression of FOXO3a‐responsive target genes (catalase, MnSOD, aP2, CD36). Thus, up‐regulating FOXO3a activity by curcumin could be a mechanism to protect against oxidant‐ and lipid‐induced damage in the inflammatory cells of the vascular system and thus reduce the risk for cardiovascular disease in the elderly. Supported by USDA Contract #58‐1950‐7‐707.