RESUMO
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.
Assuntos
Bloqueadores dos Canais de Cálcio/farmacologia , Cálcio/metabolismo , Proteína gp120 do Envelope de HIV/fisiologia , HIV-1/análise , Neurônios/efeitos dos fármacos , Animais , Células Cultivadas , Proteína gp120 do Envelope de HIV/administração & dosagem , Proteína gp120 do Envelope de HIV/antagonistas & inibidores , Hipocampo/citologia , Neurônios/metabolismo , Nimodipina/farmacologia , Ratos , Proteínas Recombinantes/farmacologia , Células Ganglionares da Retina/efeitos dos fármacos , Células Ganglionares da Retina/metabolismoRESUMO
Picomolar concentrations of native or recombinant coat protein gp120, from the human immunodeficiency virus type 1 (HIV-1), injured rat retinal ganglion cell neurons in culture. This form of neurotoxicity could be completely abrogated by anti-gp120 but not by control preimmune serum, suggesting that the lethal effects of the purified preparations of the envelope protein were due to gp120 and not to a contaminant. Entry of HIV-1 is mediated by gp120 binding to a surface protein, designated "CD4," which is located, for example, on T lymphocytes. However, in the present study, specific anti-CD4 antibodies, at concentrations known to block effects mediated by high-affinity binding to CD4 on the surface of rat T cells, did not prevent neuronal injury induced by gp120. These findings suggest that injury of central neurons engendered by gp120 may be responsible, at least in part, for the neurologic manifestations observed in as many as 2/3 of the patients with acquired immunodeficiency syndrome, such as dementia, myelopathy, and visual loss, even in the absence of superinfection. In contrast with previous studies, however, this report suggests that the deleterious effects of gp120 on neurons may not be mediated via binding to the CD4 molecule.
Assuntos
Anticorpos/imunologia , Antígenos CD4/imunologia , Anticorpos Anti-HIV/imunologia , Proteína gp120 do Envelope de HIV/efeitos adversos , HIV-1/metabolismo , Células Ganglionares da Retina/patologia , Animais , Antígenos CD4/metabolismo , Células Cultivadas , Proteína gp120 do Envelope de HIV/imunologia , Proteína gp120 do Envelope de HIV/metabolismo , Neurônios/metabolismo , Neurônios/patologia , Ligação Proteica , Ratos , Ratos Endogâmicos , Proteínas Recombinantes/efeitos adversos , Células Ganglionares da Retina/metabolismoRESUMO
Two experiments are reported in which subjects viewed films and were interrogated with questions employing the definite or the indefinite article. A significant interaction existed betweed a witness's level of neuroticism and question wording. There were also significant correlations between Neuroticism and errors resulting from questions containing the indefinite article.