Tocotrienol is the most effective vitamin E for reducing endothelial expression of adhesion molecules and adhesion to monocytes.
Alpha-tocopherol and its esterified derivatives have been shown to be effective in reducing monocytic-endothelial cell adhesion. However, the effect of alpha-tocotrienol (alpha-T3) has not been characterized. In the present study, using human umbilical vein endothelial cells (HUVEC) as the model system, we examined the relative inhibitory effects of alpha-T3 and other vitamin E derivatives on cell surface adhesion molecule expression under TNF-alpha stimulation. Using enzyme-linked immunosorbent assay, we demonstrated that alpha-T3 markedly inhibited the surface expression of vascular cell adhesion molecule-1 in TNF-alpha activated HUVEC in a dose- and time-dependent manner. The optimal inhibition was observed at 25 micromol/l alpha-T3 within 24 h (77+/-5%) without cytotoxicity. In addition, the surface expression of intercellular adhesion molecule-1 and E-selectin were also reduced by 40+/-7 and 42+/-5%, respectively. In order to further evaluate the effects of alpha-T3 on the vascular endothelium, we investigated the ability of monocytes to adhere to endothelial cells. Interestingly, a 63+/-3% decrease in monocytic cell adherence was observed. Compared to alpha-tocopherol and alpha-tocopheryl succinate, alpha-T3 displayed a more profound inhibitory effect on adhesion molecule expression and monocytic cell adherence. This inhibitory action by alpha-T3 on TNF-alpha-induced monocyte adhesion was shown to be NF-kappaB dependent and was interestingly reversed with co-incubation with farnesol and geranylgeraniol, suggesting a role for prenylated proteins in the regulation of adhesion molecule expression. In summary, the above results suggest that alpha-T3 is a potent and effective agent in the reduction of cellular adhesion molecule expression and monocytic cell adherence.
Theriault
Andre
A
Division of Medical Technology, University of Hawaii at Manoa, 1960 East-West Road, Bio C-206, Honolulu, HI 96822, USA. andret@hawaii.edu
Chao
Jun-Tzo
JT
Gapor
Abdul
A
Chao
Jun Tzo
JT
Gapor
Abeli
A
D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D019040:E-Selectin / Q000096:biosynthesis / Q000187:drug effects; D004730:Endothelium, Vascular / Q000166:cytology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis* / Q000187:drug effects*; D007375:Interleukin-1 / Q000494:pharmacology; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism*; D016328:NF-kappa B / Q000187:drug effects / Q000378:metabolism; D017368:Protein Prenylation / Q000187:drug effects; D013755:Tetradecanoylphorbol Acetate / Q000031:analogs & derivatives* / Q000494:pharmacology; D024508:Tocotrienols / Q000008:administration & dosage / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014810:Vitamin E / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology
D000975:Antioxidants; D019040:E-Selectin; D007375:Interleukin-1; D016328:NF-kappa B; D024508:Tocotrienols; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D014810:Vitamin E; C020922:4-O-methyl-12-O-tetradecanoylphorbol 13-acetate; C082032:tocotrienol, alpha; D013755:Tetradecanoylphorbol Acetate