Document 0549
 DOCN  M9650549
 TI    Iron chelation decreases NF-kappa B and HIV type 1 activation due to
       oxidative stress.
 DT    9605
 AU    Sappey C; Boelaert JR; Legrand-Poels S; Forceille C; Favier A; Piette J;
       Laboratory of Virology, University of Liege, Belgium.
 SO    AIDS Res Hum Retroviruses. 1995 Sep;11(9):1049-61. Unique Identifier :
       AIDSLINE MED/96089212
 AB    An important aspect of human immunodeficiency virus (HIV-1) infection is
       the regulation of its expression by nuclear factor kappa B (NF-kappa B)
       through redox-controlled signal transduction pathways. In this study, we
       demonstrate that iron chelation by deferoxamine (DFO) protects against
       the cytotoxic and reactivating effects of hydrogen peroxide (H2O2).
       These protective effects were observed both in lymphocytic (ACH-2) and
       promonocytic (U1) cells latently infected by HIV-1. Concomitantly,
       NF-kappa B activation by H2O2, when followed by gel retardation assay,
       was decreased in the DFO-treated U1 and ACH-2 cells. This latter
       DFO-mediated effect was specific, as DFO did not clearly affect AP-1
       DNA-binding activity when studied after H2O2-induced stress. More
       importantly, DFO protected against the H2O2-induced activation of HIV-1
       as evidenced by reverse transcriptase activity in the supernatant. DFO
       also protected against PMA-induced NF-kappa B activation as well as
       TNF-alpha-induced HIV-1 activation. Furthermore, DFO attenuated the p24
       response in PBMC infected with HIV-1 and stimulated with IL-2. These
       different effects of DFO were obtained at DFO concentrations lower than
       5 microM. Other chemically unrelated iron chelators also provided
       protection against cytotoxicity, NF-kappa B activation, and HIV-1
       activation in U1 cells challenged with H2O2.
 DE    Base Sequence  Cell Line  Deferoxamine/*PHARMACOLOGY  DNA
       Probes/GENETICS  Gene Expression Regulation/DRUG EFFECTS  Human
       Hydrogen Peroxide/PHARMACOLOGY  HIV-1/*DRUG EFFECTS/GENETICS/PHYSIOLOGY
       Iron Chelates/PHARMACOLOGY  Molecular Sequence Data  NF-kappa
       B/*BIOSYNTHESIS/GENETICS  Oxidation-Reduction  Oxidative Stress
       Siderophores/*PHARMACOLOGY  Support, Non-U.S. Gov't
       Tetradecanoylphorbol Acetate/PHARMACOLOGY  Transcription Factor
       AP-1/BIOSYNTHESIS/GENETICS  Tumor Necrosis Factor/PHARMACOLOGY  Virus
       Replication/DRUG EFFECTS  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).