Human immunodeficiency virus type 1 coat protein neurotoxicity mediated by nitric oxide in primary cortical cultures.
The human immunodeficiency virus type 1 coat protein, gp120, kills neurons in primary cortical cultures at low picomolar concentrations. The toxicity requires external glutamate and calcium and is blocked by glutamate receptor antagonists. Nitric oxide (NO) contributes to gp120 toxicity, since nitroarginine, an inhibitor of NO synthase, prevents toxicity as does deletion of arginine from the incubation medium and hemoglobin, which binds NO. Superoxide dismutase also attenuates toxicity, implying a role for superoxide anions.
Dawson
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National Institute on Drug Abuse, Addiction Research Center, Baltimore, MD 21224.
Dawson
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Uhl
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Snyder
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D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology* / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D003620:Dantrolene / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists; D005333:Fetus; D005971:Glutamates / Q000494:pharmacology; D018698:Glutamic Acid; D015699:HIV Envelope Protein gp120 / Q000633:toxicity*; D015497:HIV-1; D006454:Hemoglobins / Q000378:metabolism / Q000494:pharmacology; D007295:Inositol Phosphates / Q000378:metabolism; D008959:Models, Neurological; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D009498:Neurotoxins / Q000633:toxicity*; D009543:Nifedipine / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D019335:Nitroarginine; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats
D018691:Excitatory Amino Acid Antagonists; D005971:Glutamates; D015699:HIV Envelope Protein gp120; D006454:Hemoglobins; D007295:Inositol Phosphates; D009498:Neurotoxins; D011810:Quinoxalines; D019335:Nitroarginine; D009569:Nitric Oxide; D018698:Glutamic Acid; C056723:FG 9041; D016291:Dizocilpine Maleate; D001120:Arginine; D003620:Dantrolene; D006152:Cyclic GMP; D009543:Nifedipine; D002118:Calcium