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Genistein Protects against Tumor Necrosis Factor‐alpha‐Induced Apoptosis of Human Vascular Endothelial Cells
Author(s) -
Si Hongwei,
Liu Dongmin
Publication year - 2007
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.21.5.a373-b
Subject(s) - genistein , apoptosis , tumor necrosis factor alpha , cancer research , enos , biology , microbiology and biotechnology , pharmacology , endocrinology , chemistry , biochemistry , nitric oxide , nitric oxide synthase
Phytoestrogen genistein has an array of biological actions. However, whether it has a protective effect on vasculature is still unclear. In this study, we investigated whether genistein prevents apoptosis in endothelial cells (ECs) treated with tumor necrosis factor‐α (TNF‐α), a pro‐inflammatory cytokine associated with pathogenesis of atherosclerosis. We found that genistein at physiological doses (1–5 μM) significantly inhibited TNF‐α‐induced apoptosis of human aortic endothelial cells (HAECs) as measured by caspase‐3 activation, DNA laddering and 7‐AAD staining of apoptotic cells. The anti‐apoptotic effect of genistein is associated with increased anti‐apoptotic protein eNOS and Bcl‐2 expression that was inhibited by TNF‐α as assessed by Western blot. Genistein also enhanced the eNOS and Bcl‐2 promoter activities as determined by a luciferase reporter gene assay. Stimulation of HAECs with genistein resulted in rapid and dose‐dependent activation of Akt, a pro‐survival kinase. These findings provide the evidence that genistein acts as a survival factor for vascular ECs to protect cells against apoptosis. Preservation of thefunctional integrity of the endothelial monolayer may represent an important mechanism by which genistein exerts its vasculoprotective effect. This work was supported by the American Heart Association Mid‐Atlantic Affiliate grant (056 0565356U).