HIV-GP120 GLYCOPROTEIN STIMULATES THE INDUCIBLE ISOFORM OF NO SYNTHASE IN HUMAN CULTURED ASTROCYTOMA-CELLS

The effect of the HIV coating glycoprotein gp 120 on the generation of NO by human cultured T67 astrocytoma cells was investigated. Preincubation of astrocytoma cells with gp 120 (10 pM, 100 and 500 nM) produced a significant, dose-dependent increase of nitrite levels in supernatant of pretreated cells which was higher when compared to untreated cells. This effect was prevented by coincubation of cells with monoclonal antibodies directed against gp 120, or by pretreatment of cells with the selective NO synthase inhibitor L-NAME (100 μM). The rise of nitrite following pretreatment of astrocytoma cells with gp 120 was accompanied by an increase in NO synthase activity which was mainly Ca++-independent. Also this effect was inhibited by antibodies against gp 120, showing the specificity of the activation of the L-Arg-NO pathway subsequent to incubation of astrocytoma cells with the HIV coating protein. In conclusion, the present results are consistent with an activation of the inducible, Ca++-independent isoform of NO synthase in cultured astrocytoma cells following coincubation with gp 120. This may contribute to explain some of the neuropathological changes accompanying HIV-related cognitive disorders. © 1993 Academic Press, Inc.