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 Scopus citations

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

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine

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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, 155(1), 275-284. https://doi.org/10.1016/S0002-9440(10)65121-8