Iron chelation decreases NF-kappa B and HIV type 1 activation due to oxidative stress.

Important note: Information in this article was accurate in 1996. The state of the art may have changed since the publication date.

Iron chelation decreases NF-kappa B and HIV type 1 activation due to oxidative stress.

AIDS Res Hum Retroviruses. 1995 Sep;11(9):1049-61. Unique Identifier : AIDSLINE MED/96089212
Sappey C; Boelaert JR; Legrand-Poels S; Forceille C; Favier A; Piette J; Laboratory of Virology, University of Liege, Belgium.

Abstract: 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.

Keywords: 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
960530
M9651094

AEGiS is a 501(c)3, not-for-profit, tax-exempt, educational corporation. AEGiS is made possible through unrestricted funding from Boehringer Ingelheim, Bridgestone/Firestone Charitable Trust, Bristol-Myers Squibb Company, Elton John AIDS Foundation, Gill Foundation, the National Library of Medicine, Quest Diagnostics, Roche and Trimeris, and donations from users like you. Always watch for outdated information. This article first appeared in 1996. This material is designed to support, not replace, the relationship that exists between you and your doctor.

AEGiS presents published material, reprinted with permission and neither endorses nor opposes any material. All information contained on this website, including information relating to health conditions, products, and treatments, is for informational purposes only. It is often presented in summary or aggregate form. It is not meant to be a substitute for the advice provided by your own physician or other medical professionals. Always discuss treatment options with a doctor who specializes in treating HIV.

Copyright ©1980, 1996. AEGiS. All materials appearing on AEGiS are protected by copyright as a collective work or compilation under U.S. copyright and other laws and are the property of AEGiS, or the party credited as the provider of the content. .