Nitric Oxide Inhibits HIV Tat-Induced NF-kB Activation

Details

• Personal Author:
  Castranova, Vincent ; Chen F ; Demers LM ; Lu Y ; Rojanasakul Y ; Shi-Xiaglin S ; Vallyathan V
• Description:
  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. [Description provided by NIOSH]
• Subjects:
  Antigens Carcinogens Immune System Microbiology Occupational Health Safety Viral Diseases
• Keywords:
  Carcinogenesis Immune-reaction Immune-system-disorders In-vitro-studies Microorganisms Viral-infections
• ISSN:
  0002-9440
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 3 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  275-284
• Volume:
  155
• Issue:
  1
• NIOSHTIC Number:
  nn:20000965
• Citation:
  Am J Pathol 1999 Jul; 155(1):275-284
• Contact Point Address:
  Dr. Fei Chen, Pathology and Physiology Research Branch, NIOSH, 1095 Willowdale Road, Morgantown, WV 26505
• Email:
  lfd3@cdc.gov
• CAS Registry Number:
  Nitric oxide (CAS RN 10102-43-9)
• Federal Fiscal Year:
  1999
• Peer Reviewed:
  True
• Source Full Name:
  The American Journal of Pathology
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:449606f69254c7bfe7406811d225315263e2358522902bc3f051b4431a54c9d85f171d2953f594e50f235cf9fa8dd9d52167a7d48656d34a66c650b88a296a82
• Download URL:
  https://stacks.cdc.gov/view/cdc/198277/cdc_198277_DS1.pdf
• File Type:
  [PDF - 380.64 KB ]