Direct cytotoxicity of HIV-1 envelope protein gp120 on human NT neurons.
A new in vitro system comprising a pure population of neurons, human NT cells, was used to characterize the direct neurotoxic effect of HIV-1 envelope protein gp120. Cytotoxicity was monitored by a quantitative assay after exposure to recombinant gp120 in the presence or absence of other reagents. Treatment of mature NT neurons with various doses of gp120 for 24 h caused a decrease of up to 27% in the number of viable cells. This neurotoxicity was abolished by co-treatment with either D-2-amino-5-phosphonopentanoic acid (APV), MK801 or nimodipine, or by culturing cells in a Ca(2+)-free environment. Taken together, these data indicate that gp120 exerts a direct neurotoxic effect by acting through NMDA receptors and Ca2+ channels.
Wu
P
P
Division of Hematology/Oncology, New England Deaconess Hospital, MA 02215, USA.
Price
P
P
Du
B
B
Hatch
W C
WC
Terwilliger
E F
EF
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D015699:HIV Envelope Protein gp120 / Q000633:toxicity*; D015497:HIV-1; D006801:Humans; D009474:Neurons / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists; D011994:Recombinant Proteins / Q000633:toxicity; D014407:Tumor Cells, Cultured
D018690:Excitatory Amino Acid Agonists; D015699:HIV Envelope Protein gp120; D018696:Neuroprotective Agents; D016194:Receptors, N-Methyl-D-Aspartate; D011994:Recombinant Proteins; D016291:Dizocilpine Maleate; D015763:2-Amino-5-phosphonovalerate