INHIBITION OF NF-KAPPA-B ACTIVATION BY VITAMIN-E DERIVATIVES

Nuclear factor κB (NF-κB) 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-κB 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-α (TNF-α) induced NF-κB activation. Incubation of human Jurkat T cells with vitamin E acetate or α-tocopheryl succinate (10 μM to 1 mM) exhibited a concentration dependent inhibition of NF-κB activation, α-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-κB activation at 10 μM. Oct-1 binding activity was inactivated by α-tocopheryl succinate whereas other derivatives had no effects, suggesting that the effects of α-tocopheryl succinate are not specific to NF-κB. HPLC measurements demonstrated that treatment of cells with TNF-α had no effects on cellular α-tocopherol, but vitamin E acetate treatment increased the α-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. © 1993 Academic Press, Inc.