Immediate and neurotoxic effects of HIV protein gp120 act through CXCR4 receptor.
Primary rat hippocampal neurones show pronounced elevations of intracellular calcium within minutes of exposure to the HIV coat protein gp120. Culture of hippocampal neurones with gp120 causes significant neurotoxicity. We find that the peptide VSLSYRCPCRFF, a competitive inhibitor of the CXCR4 chemokine receptor, markedly inhibits toxicity and eliminates the acute calcium elevation. CXCR4 receptors are thought to signal to the Gi/Go family of trimeric GTP binding proteins. Pretreatment of hippocampal neurones with pertussis toxin to inactivate Gi/Go proteins markedly reduced gp120 neurotoxicity. These results indicate that both short and long term effects of gp120 are the result of activation of the CXCR4 receptor.
Pandey
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Department of Physiology, University College London, Gower Street, London, WC1E 6BT, United Kingdom.
Bolsover
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D000818:Animals; D002118:Calcium / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects; D006160:Guanosine Triphosphate / Q000378:metabolism; D015699:HIV Envelope Protein gp120 / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects*; D010455:Peptides / Q000494:pharmacology; D037342:Pertussis Toxin; D051381:Rats; D019718:Receptors, CXCR4 / Q000378:metabolism*; D013050:Spectrometry, Fluorescence; D013997:Time Factors; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D015699:HIV Envelope Protein gp120; D010455:Peptides; D019718:Receptors, CXCR4; D010566:Virulence Factors, Bordetella; D006160:Guanosine Triphosphate; D037342:Pertussis Toxin; D002118:Calcium