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PMID: 8097316 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Human immunodeficiency virus type 1 coat protein neurotoxicity mediated by nitric oxide in primary cortical cultures.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 90 ·No. 8 ·1993-04-15 ·Pages 3256-9

Dawson VL, Dawson TM, Uhl GR, Snyder SH

Abstract

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.

MeSH Terms
Animals Arginine/analogs & derivatives,pharmacology Calcium/pharmacology Cell Death/drug effects Cell Survival/drug effects Cells, Cultured Cerebral Cortex/cytology,metabolism Cyclic GMP/metabolism Dantrolene/pharmacology Dizocilpine Maleate/pharmacology Excitatory Amino Acid Antagonists Fetus Glutamates/pharmacology Glutamic Acid HIV Envelope Protein gp120/toxicity HIV-1 Hemoglobins/metabolism,pharmacology Inositol Phosphates/metabolism Models, Neurological Neurons/cytology,drug effects,metabolism Neurotoxins/toxicity Nifedipine/pharmacology Nitric Oxide/metabolism Nitroarginine Quinoxalines/pharmacology Rats
Chemicals
Excitatory Amino Acid Antagonists Glutamates HIV Envelope Protein gp120 Hemoglobins Inositol Phosphates Neurotoxins Quinoxalines Nitroarginine Nitric Oxide Glutamic Acid FG 9041 Dizocilpine Maleate Arginine Dantrolene Cyclic GMP Nifedipine Calcium
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Dawson V L
National Institute on Drug Abuse, Addiction Research Center, Baltimore, MD 21224.
Dawson T M
Uhl G R
Snyder S H
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.90.8.3256
Published
1993-04-15
Pages
3256-9
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC46278
Subset
IM
Grants
NIDA NIH HHS · DA-00074 · United States
NIDA NIH HHS · DA-00266 · United States
NIDA NIH HHS · DA-271-90-7408 · United States
External Links
PubMed source DOI: 10.1073/pnas.90.8.3256 PMC Full Text View journal details
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