liu.seSearch for publications in DiVA
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Hiv-1 Tat Potentiates Tnf-Induced Nf-Kappa-B Activation and Cytotoxicity
Division of Immunogenetics, German Cancer Research Center, Heidelberg..
Division of Immunogenetics, German Cancer Research Center, Heidelberg..
Division of Immunogenetics, German Cancer Research Center, Heidelberg. Germany .
Division of Immunogenetics, German Cancer Research Center, Heidelberg..
Show others and affiliations
1995 (English)In: EMBO Journal, ISSN 0261-4189, E-ISSN 1460-2075, Vol. 14, no 3, 546-554 p.Article in journal (Refereed) Published
Abstract [en]

This study demonstrates that human immunodeficiency virus type 1 (HTV-1) Tat protein amplifies the activity of tumor necrosis factor (TNF), a cytokine that stimulates HTV-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 (Tat(1-72)), 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. They further imply a distinct mechanism of Mn-SOD suppression as compared,vith HIV-1 LTR transactivation by Tat. Taken together, our data suggest that Tat expressed in HIV-1-infected cells and Tat taken up by non-infected cells modulates TNF activity by altering the cellular redox state. These findings may be relevant for HIV-1 replication and for T cell depletion in acquired immune deficiency syndrome.

Place, publisher, year, edition, pages
1995. Vol. 14, no 3, 546-554 p.
Keyword [en]
aids patients, cyto-toxicity, cytotoxicity, dna-binding, factor-alpha, human-immunodeficiency-virus, long terminal repeat, mn-sod, nf-kappa-b activation, superoxide-dismutase, tat, TNF, trans-activation, transcription factor, tumor-necrosis-factor
National Category
Biochemistry and Molecular Biology Cell Biology
Identifiers
URN: urn:nbn:se:liu:diva-87081ISI: A1995QF71800014OAI: oai:DiVA.org:liu-87081DiVA: diva2:584846
Available from: 2013-01-09 Created: 2013-01-09 Last updated: 2017-12-06

Open Access in DiVA

fulltext(626 kB)178 downloads
File information
File name FULLTEXT01.pdfFile size 626 kBChecksum SHA-512
8d67c914fb77c465a2c344f0c25a3c74f65a6f705fb24103868f1ddffcab22156f1cb817034705d3b6f13dab521f51f902f93903f22349acb80655f61593be69
Type fulltextMimetype application/pdf

Authority records BETA

Los, Marek Jan

Search in DiVA

By author/editor
Los, Marek Jan
In the same journal
EMBO Journal
Biochemistry and Molecular BiologyCell Biology

Search outside of DiVA

GoogleGoogle Scholar
Total: 178 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

urn-nbn

Altmetric score

urn-nbn
Total: 555 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf