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HIV-1 Tat potentiates TNF-induced NF-kappa B activation and cytotoxicity by altering the cellular redox state.

1995; Springer Nature; Volume: 14; Issue: 3 Linguagem: Inglês

10.1002/j.1460-2075.1995.tb07030.x

1460-2075

Michael O. Westendorp, В. А. Шатров, Klaus Schulze‐Osthoff, Rainer Frank, Margot Kraft, Marek Łoś, Peter H. Krammer, Wulf Dröge, V. Lehmann,

T-cell and Retrovirus Studies

Research Article1 February 1995free access HIV-1 Tat potentiates TNF-induced NF-kappa B activation and cytotoxicity by altering the cellular redox state. M.O. Westendorp M.O. Westendorp Division of Immunogenetics, German Cancer Research Center, Heidelberg. Search for more papers by this author V.A. Shatrov V.A. Shatrov Division of Immunogenetics, German Cancer Research Center, Heidelberg. Search for more papers by this author K. Schulze-Osthoff K. Schulze-Osthoff Division of Immunogenetics, German Cancer Research Center, Heidelberg. Search for more papers by this author R. Frank R. Frank Division of Immunogenetics, German Cancer Research Center, Heidelberg. Search for more papers by this author M. Kraft M. Kraft Division of Immunogenetics, German Cancer Research Center, Heidelberg. Search for more papers by this author M. Los M. Los Division of Immunogenetics, German Cancer Research Center, Heidelberg. Search for more papers by this author P.H. Krammer P.H. Krammer Division of Immunogenetics, German Cancer Research Center, Heidelberg. Search for more papers by this author W. Dröge W. Dröge Division of Immunogenetics, German Cancer Research Center, Heidelberg. Search for more papers by this author V. Lehmann V. Lehmann Division of Immunogenetics, German Cancer Research Center, Heidelberg. Search for more papers by this author M.O. Westendorp M.O. Westendorp Division of Immunogenetics, German Cancer Research Center, Heidelberg. Search for more papers by this author V.A. Shatrov V.A. Shatrov Division of Immunogenetics, German Cancer Research Center, Heidelberg. Search for more papers by this author K. Schulze-Osthoff K. Schulze-Osthoff Division of Immunogenetics, German Cancer Research Center, Heidelberg. Search for more papers by this author R. Frank R. Frank Division of Immunogenetics, German Cancer Research Center, Heidelberg. Search for more papers by this author M. Kraft M. Kraft Division of Immunogenetics, German Cancer Research Center, Heidelberg. Search for more papers by this author M. Los M. Los Division of Immunogenetics, German Cancer Research Center, Heidelberg. Search for more papers by this author P.H. Krammer P.H. Krammer Division of Immunogenetics, German Cancer Research Center, Heidelberg. Search for more papers by this author W. Dröge W. Dröge Division of Immunogenetics, German Cancer Research Center, Heidelberg. Search for more papers by this author V. Lehmann V. Lehmann Division of Immunogenetics, German Cancer Research Center, Heidelberg. Search for more papers by this author Author Information M.O. Westendorp1, V.A. Shatrov1, K. Schulze-Osthoff1, R. Frank1, M. Kraft1, M. Los1, P.H. Krammer1, W. Dröge1 and V. Lehmann1 1Division of Immunogenetics, German Cancer Research Center, Heidelberg. The EMBO Journal (1995)14:546-554https://doi.org/10.1002/j.1460-2075.1995.tb07030.x PDFDownload PDF of article text and main figures. ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinked InMendeleyWechatReddit Figures & Info This study demonstrates that human immunodeficiency virus type 1 (HIV-1) Tat protein amplifies the activity of tumor necrosis factor (TNF), a cytokine that stimulates HIV-1 replication through activation of NF-kappa B. In HeLa cells stably transfected with the HIV-1 tat gene (HeLa-tat cells), expression of the Tat protein enhanced both TNF-induced activation of NF-kappa B and TNF-mediated cytotoxicity. A similar potentiation of TNF effects was observed in Jurkat T cells and HeLa cells treated with soluble Tat protein. TNF-mediated activation of NF-kappa B and cytotoxicity involves the intracellular formation of reactive oxygen intermediates. Therefore, Tat-mediated effects on the cellular redox state were analyzed. In both T cells and HeLa cells HIV-1 Tat suppressed the expression of Mn-dependent superoxide dismutase (Mn-SOD), a mitochondrial enzyme that is part of the cellular defense system against oxidative stress. Thus, Mn-SOD RNA protein levels and activity were markedly reduced in the presence of Tat. Decreased Mn-SOD expression was associated with decreased levels of glutathione and a lower ratio of reduced:oxidized glutathione. A truncated Tat protein (Tat1-72), known to transactivate the HIV-1 long terminal repeat (LTR), no longer affected Mn-SOD expression, the cellular redox state or TNF-mediated cytotoxicity. Thus, our experiments demonstrate that the C-terminal region of HIV-1 Tat is required to suppress Mn-SOD expression and to induce pro-oxidative conditions reflected by a drop in reduced glutathione (GSH) and the GSH:oxidized GSH (GSSG) ratio.(ABSTRACT TRUNCATED AT 250 WORDS) Previous ArticleNext Article Volume 14Issue 31 February 1995In this issue RelatedDetailsLoading ...