Important note: Information in this article was accurate in 1993. The state of the art may have changed since the publication date.
The effect of antioxidants on the activation of the transcription activator NF-kappa B by transactivators from hepatitis B virus and HTLV-1 (Meeting abstract).
International Symposium on Cancer, Sapporo Cancer Seminar: Oxyradicals and Anti-oxidative Responses in Cancer. July 14-16, 1992, Sapporo, Japan, p. 43, 1992.. Unique Identifier : AIDSLINE ICDB/93690044 Baeuerle PA; Schreck R; Meyer M; Schluter V; Caselmann W; Hofschneider PH; Gene Center, Ludwig-Maximilians Univ., Munich, Germany
Abstract:
The nuclear factor kappa B (NF-kappa B) is an inducible transcription factor that is activated when cells are exposed to TNF, IL-1, viruses, double-stranded RNA, lipopolysaccharide, UV light and gamma rays. A hallmark of NF-kappa B is that, in nonstimulated cells, it resides in the cytoplasm in complex with the inhibitory subunit I kappa B. Stimulation of cells results in release of I kappa B, nuclear transport of NF-kappa B and, finally, binding of NF-kappa B to promoter and enhancer elements in genes, an event causing the initiation of mRNA synthesis from many cytokine genes. TNF is known to induce the production of superoxide and H2O2 in cells. This prompted us to test whether H2O2 itself is capable of inducing NF-kappa B. Micromolar concentrations of H2O2 could indeed potently activate NF-kappa B in a human T-cell line, and the activation was blocked by N-acetyl-L-cysteine (NAC), dithiocarbamates (DTCs) and nonsulfur iron/copper chelators. Various antioxidants also blocked induction of NF-kappa B by TNF and by all other inducers of NF-kappa B tested so far. These results suggest that reactive oxygen intermediates (ROI) play a role as messengers or modulators in the activation of NF-kappa B. Some tumorigenic viruses activate NF-kappa B through expression of proteins with transactivating activity. Examples are the Tax protein from HTLV-1, the X protein from HBV and truncated forms of the middle surface antigen from HBV, referred to as MHBs(t). These three proteins have pleiotropic activity; they not only activate NF-kappa B but also a series of other host transcription factors. Using antioxidants, we have tested whether the activation of NF-kappa B by the viral proteins follows unique pathways or is also dependent on the production of ROI. NAC and DTCs potently suppressed transactivation and NF-kappa B induction by Tax, X and MHBs(t), while other transactivating activities of the proteins were not affected. It thus appears that the viral proteins elicit a cellular stress program in the course of which NF-kappa B is induced via oxidative stress. We discuss the possibility that increased levels of ROI induced by viral transactivators are related to the tumorigenic potential of the proteins. (6 Refs)
Keywords: Antioxidants/*PHARMACOLOGY Gene Products, tax/METABOLISM Hepatitis B Antigens/METABOLISM Hepatitis B Virus/*METABOLISM Hydrogen Peroxide/PHARMACOLOGY HTLV-I/*METABOLISM NF-kappa B/*METABOLISM Trans-Activators/*METABOLISM ABSTRACT 930430
M9340824
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Important note: Information in this article was accurate in 1993. The state of the art may have changed since the publication date.
