Inhibition of NF-kappa B activation by vitamin E derivatives.
Nuclear factor kappa B (NF-kappa B) is believed to play an important role in the activation of a human immunodeficiency virus (HIV) which causes acquired immunodeficiency syndrome (AIDS). Recent findings suggesting an involvement of reactive oxygen species in signal transduction pathways leading to NF-kappa B activation have ensured the possible clinical use of antioxidants in blocking HIV activation. The present study examined the effects of vitamin E derivatives on the tumor necrosis factor-alpha (TNF-alpha) induced NF-kappa B activation. Incubation of human Jurkat T cells with vitamin E acetate or alpha-tocopheryl succinate (10 microM to 1 mM) exhibited a concentration dependent inhibition of NF-kappa B activation. alpha-Tocopherol or succinate at these concentrations had no apparent effects. 2,2,5,7,8-Pentamethyl-6-hydroxychromane (PMC) was extremely effective, causing complete inhibition of NF-kappa B activation at 10 microM. Oct-1 binding activity was inactivated by alpha-tocopheryl succinate whereas other derivatives had no effects, suggesting that the effects of alpha-tocopheryl succinate are not specific to NF-kappa B. HPLC measurements demonstrated that treatment of cells with TNF-alpha had no effects on cellular alpha-tocopherol, but vitamin E acetate treatment increased the alpha-tocopherol content. Cell viability was not affected by any of the vitamin E derivatives. These results indicate a possible use of vitamin E derivatives in AIDS therapeutics.
Department of Molecular & Cell Biology, University of California, Berkeley 94720.
Y J
YJ
Suzuki
L
L
Packer
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D016328:NF-kappa B / Q000378:metabolism*; D051381:Rats; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism; D014810:Vitamin E / Q000031:analogs & derivatives / Q000494:pharmacology* / Q000627:therapeutic use
D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D014810:Vitamin E