title: NF-kappa B-independent suppression of HIV expression by ascorbic acid.
abstract: Ascorbic acid (ascorbate or vitamin C) has been shown to suppress the induction of HIV in latently infected T lymphocytic cells following stimulation with a tumor promoter (PMA) and inflammatory cytokine (TNF-alpha). To assess whether this inhibition was mediated via modulation of the cellular transcription factor, NF-kappa B, we carried out gel shift analysis on nuclear extracts prepared under different conditions of cell stimulation in the presence or absence of ascorbate, N-acetylcysteine (NAC), or zidovudine (AZT). Pretreatment of ACH-2 T cells by NAC followed by stimulation with PMA, TNF-alpha, or hydrogen peroxide (H2O2) resulted in strong suppression of NF-kappa B activation. In contrast, neither ascorbate nor AZT affected NF-kappa B activity under all three induction conditions in the ACH-2 cell line. Ascorbate and AZT also had no effect on NF-kappa B activation following TNF-alpha- or PMA-induced stimulation of U1 promonocytic cells. These results suggest that the molecular mechanism of HIV inhibition by ascorbate is not mediated via NF-kappa B inhibition, unlike that seen with other antioxidants.
authors.affiliation: Linus Pauling Institute of Science and Medicine, Palo Alto, California 94306, USA.
authors.forename: S
authors.initials: S
authors.lastname: Harakeh
authors.forename: R J
authors.initials: RJ
authors.lastname: Jariwalla
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D001205:Ascorbic Acid / Q000494:pharmacology*; D002460:Cell Line; D006678:HIV / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D016328:NF-kappa B / Q000378:metabolism*; D013601:T-Lymphocytes / Q000821:virology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D017735:Virus Latency; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D006861:Hydrogen Peroxide; D013755:Tetradecanoylphorbol Acetate; D001205:Ascorbic Acid; D000111:Acetylcysteine