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Nitric oxide inhibits HIV tat-induced NF-kB activation.

Authors
Chen-F; Lu-Y; Castranova-V; Rojanasakul-Y; Vallyathan-V; Shi-Xiaglin-S; Demers-LM
Source
Am J Pathol 1999 Jul; 155(1):275-284
NIOSHTIC No.
20000965
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)-kappaB, a key transcription factor involved in HIV gene expression and viral replication. In the present study, we demonstrate that HIV Tat activates NF-kappaB 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-kappaB activity. In addition, NO attenuates signal-initiated degradation of IkappaBalpha, an intracellular inhibitor of NF-kappaB, and blocks the DNA binding activity of the NF-kappaB 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-kappaB 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-kappaB site is not of primary importance. Rather, several Sp-1 sites adjoining the putative NF-kappaB binding site in the promoter region of NOS-3 gene are required for the induction of NOS-3 gene expression by Tat.
Keywords
Immune-reaction; Carcinogenesis; Immune-system-disorders; Microorganisms; Antigens; In-vitro-studies; Viral-infections
CODEN
AJPAA4
CAS No.
10102-43-9
Publication Date
19990701
Document Type
Journal Article
Fiscal Year
1999
NTIS Accession No.
NTIS Price
Issue of Publication
1
ISSN
0002-9440
NIOSH Division
HELD
Source Name
American Journal of Pathology
State
WV
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