HIV-1 coat protein neurotoxicity prevented by calcium channel antagonists.
Coat protein gp120 from the human immunodeficiency virus type-1 (HIV-1) increased intracellular free calcium and injured rodent retinal ganglion cells and hippocampal neurons in culture. Highly purified recombinant gp120 envelope protein produced these effects in a dose-dependent fashion at picomolar concentrations. Immunoprecipitation with antibody to gp120, but not with control immunoglobulin-containing serum, depleted solutions of the viral envelope protein and also prevented both the rise in intracellular calcium and neuronal toxicity. The gp120-induced increase in intracellular calcium was abrogated by transiently lowering extracellular calcium or by adding the dihydropyridine calcium channel antagonist nimodipine (100 nM). Calcium channel antagonists also prevented gp120-induced neuronal injury. In addition, intracellular stores appeared to contribute substantially to the increase in calcium elicited by gp120. Since increases in intracellular calcium have been associated with neurotoxicity, it is possible that an injurious effect of gp120 on neurons might be related to this mechanism and that treatment with calcium channel antagonists may prove useful in mitigating HIV-1-related neuronal injury.
Dreyer
E B
EB
Department of Neurology, Children's Hospital, Boston, MA.
Kaiser
P K
PK
Offermann
J T
JT
Lipton
S A
SA
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002478:Cells, Cultured; D015699:HIV Envelope Protein gp120 / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000502:physiology*; D015497:HIV-1 / Q000032:analysis*; D006624:Hippocampus / Q000166:cytology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D009553:Nimodipine / Q000494:pharmacology; D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000378:metabolism
D002121:Calcium Channel Blockers; D015699:HIV Envelope Protein gp120; D011994:Recombinant Proteins; D009553:Nimodipine; D002118:Calcium