Inhibition of NF‐_κB transcriptional activity by α‐tocopheryl succinate

Abstract

The role of vitamin E in cell regulation in addition to its function as an antioxidant has attracted attention. The effects of alpha-tocopherol (T) and alpha-tocopheryl succinate (TS) on transcriptional activation of the tumor necrosis factor alpha (TNF-alpha) gene and nuclear factor kappa B (NF-kappa B) activation were examined. Two stable transformants were used: TR-1 cells derived from THP-1 cells transfected with a vector contains the human TNF-alpha promoter (1.4-kb) joined to the human placental alkaline phosphatase (PLAP) coding sequence, and B164 cells derived from the same cell line but carrying the vector containing the human beta-actin promoter (4.3-kb) as a control. The transfectants were cultured in the presence of TS, followed by stimulation with lipopolysaccharide (LPS). After stimulation, PLAP activity secreted into the culture medium was measured. TS reduced TNF-alpha transcriptional activity in a concentration-dependent manner, while no effect was observed on that of the beta-actin promoter. Gel shift assay revealed that THP-1 cells pretreated with TS and then with LPS showed inhibition of NF-kappa B activity by 43% at 50 microM versus the TS-untreated group. Since TS did not affect activator protein-1 (AP-1) activity under the same conditions, the inhibitory effect of TS on NF-kappa B activation might be specific. However, T had no effect on the results of the gel shift assay. Vitamin E transportation was analyzed by simultaneous determination of vitamin E and its derivatives using HPLC. The vitamin E recovered from culture pellets showed almost the same amounts of T and TS transferred and was recovered in unchanged form. These observations indicated that TS inhibited NF-kappa B activation and/or translocation to the nuclei in its unchanged form under the culture conditions used here. These results suggested that vitamin E is involved in signal transduction via an effect distinct from its antioxidant function. To explain the lack of activity with T, it remains to be clarified whether physiological incorporation of T occurred.

Red Wine Intake Prevents Nuclear Factor-κB Activation in Peripheral Blood Mononuclear Cells of Healthy Volunteers During Postprandial Lipemia

“…In addition, 2 antioxidant compounds present in red wine, quercetin and ␣-tocopherol succinate, inhibited this activation, and ethanol did not modify NF-B activation induced by VLDL (not shown). In this sense, ␣-tocopherol succinate, a vitamin E derivative, inhibits NF-B activation in Thp-1 cells induced by lipopolysaccharide, 38 and quercetin inhibits interleukin-8 and monocyte chemoattractant protein-1 expression in synoviocytes. 39 However, Wadsworth et al 40 reported that quercetin and resveratrol did not inhibit lipopolysaccharide-induced activation of NF-B in RAW 264.7 cells.…”

Roles of Reactive Oxygen Species, NF-κB, and Peroxiredoxins in Glycochenodeoxycholic Acid-Induced Rat Hepatocytes Death

“…ROS are known to be potent activators of the nuclear transcriptional factor, NF-ÎB [4], while the addition of antioxidants such as vitamin E or the overexpression of antioxidant enzymes such as glutathione peroxidase can block activation of the transcriptional factor [5,6]. In addition, increased NF-ÎB expression has been linked to ROS-induced cell death [7].…”

Inflammation: the foundation of diseases and disorders. A review of phytomedicines of South African origin used to treat pain and inflammatory conditions.

“…In addition, some constituents are free radical scavengers (Cos et al, 1998) and are therefore able to reduce tissue damage caused by oxidation stress of superoxide, hydroxyl and lipid peroxidation products. Green tea polyphenols, curcumin, and resveratrol inhibit the activation of NF B and also have antioxidant activity (Nakamura et al, 1998;Shishodia et al, 2003). They are considered as moderate antiinflammatory agents and could be used for preventive therapy and perhaps as therapeutics for the treatment of inflammation related diseases (Yamamoto and Gaynor, 2001).…”