Document 0251
 DOCN  M9650251
 TI    HIV-1 envelope proteins gp120 and gp160 potentiate NMDA-induced [Ca2+]i
       increase, alter [Ca2+]i homeostasis and induce neurotoxicity in human
       embryonic neurons.
 DT    9605
 AU    Lannuzel A; Lledo PM; Lamghitnia HO; Vincent JD; Tardieu M; Laboratoire
       de Neurovirologie et Neuroimmunologie, UFR; Kremlin-Bicetre, Universite
       Paris XI, Le Kremlin-Bicetre,; France.
 SO    Eur J Neurosci. 1995 Nov 1;7(11):2285-93. Unique Identifier : AIDSLINE
       MED/96149639
 AB    The envelope glycoprotein gp120 of the human immunodeficiency virus
       HIV-1 has been proposed to cause neuron death in developing murine
       hippocampal cultures and rat retinal ganglion cells. In the present
       study, cultured human embryonic cerebral and spinal neurons from 8- to
       10-week-old embryos were used to study the neurotoxic effect of gp120
       and gp160. Electrophysiological properties as well as
       N-methyl-D-aspartate (NMDA)-induced current were recorded from neurons
       maintained in culture for 10-30 days. Neither voltage-activated sodium
       or calcium currents nor NMDA-induced currents were affected by exposure
       of neurons to 250 pM gp120 or gp160. In contrast, when neurons were
       subjected to photometric measurements using the calcium dye indo-1 to
       monitor the intracellular free Ca2+ concentration ([Ca2+])i, gp120 and
       gp160 (20-250 pM) potentiated the large rises in [Ca2+]i induced by 50
       microM NMDA. The potentiation of NMDA-induced Ca2+ responses required
       the presence of Ca2+ in the medium, and was abolished by the NMDA
       antagonist D-2-amino-5-phosphonovalerate (AP5) and the voltage-gated
       Ca2+ channel inhibitor nifedipine. Moreover, exposure of a subpopulation
       of spinal neurons (25% of the cells tested) to 20-250 pM gp120 or gp160
       resulted in an increase in [Ca2+]i that followed three patterns:
       fluctuations not affected by AP5, a single peak, and the progressive and
       irreversible rise of [Ca2+]i. The neurotoxicity of picomolar doses of
       gp120 and gp160 cultures was estimated by immunofluorescence and
       colorimetric assay. Treatment of cultures with AP5 or nifedipine reduced
       gp120-induced toxicity by 70 and
 DE    Calcium/*METABOLISM  Cells, Cultured  Homeostasis/DRUG
       EFFECTS/PHYSIOLOGY  Human  HIV Envelope Protein gp120/*PHARMACOLOGY
       Membrane Potentials/DRUG EFFECTS/PHYSIOLOGY
       N-Methylaspartate/*PHARMACOLOGY  Neurons/*DRUG EFFECTS/PHYSIOLOGY
       Patch-Clamp Techniques  Prosencephalon/DRUG EFFECTS/PHYSIOLOGY  Spinal
       Cord/DRUG EFFECTS/PHYSIOLOGY  Support, Non-U.S. Gov't  Time Factors
       JOURNAL ARTICLE

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