Nitric oxide inhibits HIV Tat-induced NF-κB activation

Fei Chen, Yongju Lu, Vince Castranova, Yon Rojanasakul, Kaoru Miyahara, Yutaka Shizuta, Val Vallyathan, Xianglin Shi, Laurence Demers

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

To evaluate the roles of nitric oxide (NO) on human immunodeficiency virus (HIV) Tat-induced transactivation of HIV long terminal repeat (HIV- LTR), we examined the effect of NO in the regulation of nuclear factor (NF)- κB, a key transcription factor involved in HIV gene expression and viral replication. In the present study, we demonstrate that HIV Tat activates NF- κB and that this activation can be attenuated by endogenous or exogenous NO. Inhibition of endogenous NO production with the NO synthase (NOS) inhibitor L-NMMA causes a significant increase in Tat-induced NF-κB activity. In addition, NO attenuates signal-initiated degradation of IκBα, an intracellular inhibitor of NF-κB, and blocks the DNA binding activity of the NF-κB p50/p50 homodimer and p50/p65 heterodimer. To determine how NO is induced by HIV Tat, reverse transcription polymerase chain reaction was used to demonstrate the induction of NOS-2 and NOS-3 mRNA by Tat. Although a putative NF-κB binding site was identified in the -74 GGAGAGCCCCC -64 region of the NOS-3 gene promoter, gel mobility shift assays and site-directed mutation analyses suggest that the putative NF-κB site is not of primary importance. Rather, several Sp-1 sites adjoining the putative NF-κB binding site in the promoter region of NOS-3 gene are required for the induction of NOS-3 gene expression by Tat.

Original languageEnglish (US)
Pages (from-to)275-284
Number of pages10
JournalAmerican Journal of Pathology
Volume155
Issue number1
DOIs
StatePublished - Jan 1 1999

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Nitric Oxide Synthase
Nitric Oxide
HIV
Binding Sites
HIV Long Terminal Repeat
Gene Expression
omega-N-Methylarginine
Electrophoretic Mobility Shift Assay
Genetic Promoter Regions
Transcriptional Activation
Genes
Reverse Transcription
Transcription Factors
Gels
Polymerase Chain Reaction
Messenger RNA
Mutation
DNA

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine

Cite this

Chen, F., Lu, Y., Castranova, V., Rojanasakul, Y., Miyahara, K., Shizuta, Y., ... Demers, L. (1999). Nitric oxide inhibits HIV Tat-induced NF-κB activation. American Journal of Pathology, 155(1), 275-284. https://doi.org/10.1016/S0002-9440(10)65121-8
Chen, Fei ; Lu, Yongju ; Castranova, Vince ; Rojanasakul, Yon ; Miyahara, Kaoru ; Shizuta, Yutaka ; Vallyathan, Val ; Shi, Xianglin ; Demers, Laurence. / Nitric oxide inhibits HIV Tat-induced NF-κB activation. In: American Journal of Pathology. 1999 ; Vol. 155, No. 1. pp. 275-284.
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Chen, F, Lu, Y, Castranova, V, Rojanasakul, Y, Miyahara, K, Shizuta, Y, Vallyathan, V, Shi, X & Demers, L 1999, 'Nitric oxide inhibits HIV Tat-induced NF-κB activation', American Journal of Pathology, vol. 155, no. 1, pp. 275-284. https://doi.org/10.1016/S0002-9440(10)65121-8

Nitric oxide inhibits HIV Tat-induced NF-κB activation. / Chen, Fei; Lu, Yongju; Castranova, Vince; Rojanasakul, Yon; Miyahara, Kaoru; Shizuta, Yutaka; Vallyathan, Val; Shi, Xianglin; Demers, Laurence.

In: American Journal of Pathology, Vol. 155, No. 1, 01.01.1999, p. 275-284.

Research output: Contribution to journalArticle

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AU - Lu, Yongju

AU - Castranova, Vince

AU - Rojanasakul, Yon

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AU - Shizuta, Yutaka

AU - Vallyathan, Val

AU - Shi, Xianglin

AU - Demers, Laurence

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Chen F, Lu Y, Castranova V, Rojanasakul Y, Miyahara K, Shizuta Y et al. Nitric oxide inhibits HIV Tat-induced NF-κB activation. American Journal of Pathology. 1999 Jan 1;155(1):275-284. https://doi.org/10.1016/S0002-9440(10)65121-8