Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 1992 May 1;175(5):1181-94.
doi: 10.1084/jem.175.5.1181.

Dithiocarbamates as potent inhibitors of nuclear factor kappa B activation in intact cells

R Schreck  1 , B Meier, D N Männel, W Dröge, P A Baeuerle
Affiliations

Dithiocarbamates as potent inhibitors of nuclear factor kappa B activation in intact cells

R Schreck et al. J Exp Med. .

Abstract

Dithiocarbamates and iron chelators were recently considered for the treatment of AIDS and neurodegenerative diseases. In this study, we show that dithiocarbamates and metal chelators can potently block the activation of nuclear factor kappa B (NF-kappa B), a transcription factor involved in human immunodeficiency virus type 1 (HIV-1) expression, signaling, and immediate early gene activation during inflammatory processes. Using cell cultures, the pyrrolidine derivative of dithiocarbamate (PDTC) was investigated in detail. Micromolar amounts of PDTC reversibly suppressed the release of the inhibitory subunit I kappa B from the latent cytoplasmic form of NF-kappa B in cells treated with phorbol ester, interleukin 1, and tumor necrosis factor alpha. Other DNA binding activities and the induction of AP-1 by phorbol ester were not affected. The antioxidant PDTC also blocked the activation of NF-kappa B by bacterial lipopolysaccharide (LPS), suggesting a role of oxygen radicals in the intracellular signaling of LPS. This idea was supported by demonstrating that treatment of pre-B and B cells with LPS induced the production of O2- and H2O2. PDTC prevented specifically the kappa B-dependent transactivation of reporter genes under the control of the HIV-1 long terminal repeat and simian virus 40 enhancer. The results from this study lend further support to the idea that oxygen radicals play an important role in the activation of NF-kappa B and HIV-1.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Proc Natl Acad Sci U S A. 1990 Dec;87(24):9943-7 - PubMed
    1. Free Radic Res Commun. 1986;2(1-2):125-7 - PubMed
    1. J Biol Chem. 1991 Jun 25;266(18):11421-4 - PubMed
    1. Biochem J. 1979 Nov 15;184(2):469-72 - PubMed
    1. Cell. 1986 Dec 26;47(6):921-8 - PubMed

Publication types

  NODES
Idea 2
idea 2
twitter 2