Document 0869
 DOCN  M9650869
 TI    Death of cultured human neuroblastoma cells induced by HIV-1 gp120 is
       prevented by NMDA receptor antagonists and inhibitors of nitric oxide
       and cyclooxygenase.
 DT    9605
 AU    Corasaniti MT; Melino G; Navarra M; Garaci E; Finazzi-Agro A; Nistico G;
       Faculty of Pharmacy, University of Reggio Calabria, Cantanzaro,; Italy.
 SO    Neurodegeneration. 1995 Sep;4(3):315-21. Unique Identifier : AIDSLINE
       MED/96130874
 AB    The cytotoxic effects of the human immunodeficiency virus type 1 (HIV-1)
       coat protein gp120 were studied in human CHP100 neuroblastoma cell
       cultures. Incubation of neuroblastoma cultures with gp120 (1 pM-10 nM)
       induces cell death which is not concentration-related. The significant
       cell death evoked by 10 pM gp120 was prevented by neutralization of the
       viral protein with a monoclonal anti-gp120 (IgG) antibody. In addition,
       gp120-induced cytotoxicity was inhibited by
       [DL-(E)-2-amino-4-methyl-5-phosphono-3-pentenoic acid] (CGP37849; 100
       microM), [(+/-)-3R*, 4as*, 6R*, 8aR*-6-(phosphonomethyl)
       decahydro-isoquinoline-3-carboxylic acid] (LY274614; 100 microM), MK801
       (dizocilpine; 200 nM) and 7-chloro kynurenic acid (100 microM),
       selective antagonists of the NMDA receptor complex; by contrast,
       (6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 100 microM), a non-NMDA
       antagonist, was ineffective. Prevention of the lethality elicited by the
       HIV-1 coat protein was also obtained by incubating neuroblastoma cells
       with gp120 in Ca(2+)-free medium. The lethal effects induced by gp120
       involve activation of L-arginine-nitric oxide (NO) pathway since these
       were prevented by haemoglobin (10 microM), a NO-trapping agent, and by
       D-arginine (1 mM), the less active enantiomer of the endogenous
       precursor of NO synthesis. Cytoprotection was also afforded by N
       omega-nitro-L-arginine methyl ester (L-NAME; 200 microM), an inhibitor
       of NO synthase, and this was reversed by L-arginine (1 mM).
       Interestingly, indomethacin and flufenamic acid (10 microM), two
       inhibitors of cyclooxygenase, protected neuroblastoma cells from death
       induced by gp120. Furthermore, indomethacin prevented the neuroblastoma
       cell death evoked by exposure of cultures to sodium nitroprusside (SNP;
       0.2-1.6 mM), a NO donor. Finally significant cytotoxic effects were
       observed after incubation of neuroblastoma cells with prostaglandin E2
       (0.1-10 microM). In conclusion, the present data suggest that death of
       human CHP100 neuroblastoma cells in culture produced by gp120 involves
       NO and PGE2 production.
 DE    Antineoplastic Agents/*PHARMACOLOGY  Arginine/ANALOGS &
       DERIVATIVES/PHARMACOLOGY  Cell Death/DRUG EFFECTS  Cyclooxygenase
       Inhibitors/*PHARMACOLOGY  Flufenamic Acid/PHARMACOLOGY  Human  HIV
       Envelope Protein gp120/DRUG EFFECTS/*PHARMACOLOGY
       Indomethacin/PHARMACOLOGY  Neuroblastoma/*DRUG THERAPY/PATHOLOGY  Nitric
       Oxide/*ANTAGONISTS & INHIB/PHYSIOLOGY  Nitroprusside/PHARMACOLOGY
       Prostaglandins/PHYSIOLOGY  Receptors, N-Methyl-D-Aspartate/*ANTAGONISTS
       & INHIB  Recombinant Proteins/ANTAGONISTS & INHIB  Support, Non-U.S.
       Gov't  Tumor Cells, Cultured  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).