7th International AIDS Conference Florence, Italy — June 16-21, 1991

Int Conf AIDS 1991 Jun 16-21; 7:101 (abstract no. M.A.1037)
Giulio L, Petrucci T, Patrizio M, Bernardo A; Istituto Superiore di Santia, Pathophysiol, and Cell Biol. Labs, Roma, Italy

OBJECTIVE: It has been hypothesized that neural cell damage responsible for the AIDS dementia complex may result from CD4-independent infection, from release of neurotoxic viral-coded products (e.g. gp120) or from exposure to products (cytokines or others) derived from infected or reactive cells. Since astrocytes, the most abundant neural cells in the CNS, are believed to exert a fine control on neural cell function and are directly or indirectly involved in most neurological diseases, our studies were aimed at testing whether interaction with the HIV envelope protein gp120 might determine functional alterations in these cells.

RESULTS: Using secondary cultures of purified type-1 astrocytes obtained from the neonatal rat cerebral cortex, we obtained the following results: exposure of the cells to 100 pM gp120 (Genentech, S. Francisco) for 10 min caused a 50-150% increase in the level of cyclic AMP which was counteracted by the beta-adrenergic antagonist propanolol. Moreover, 100 pM gp120 counteracted (by 20-60%) the 20-100 fold increase in cyclic AMP levels induced by the beta-adrenergic agonist isoproterenol (1-10 nM). Finally, exposure of the cells to 0.1-10 nM gp120 for 30 min caused alterations in the phosphorylation pattern of astroglial proteins (analyzed by bidimensional PAGE) qualitatively similar (but quantitatively lower) to those induced by 10 nM isoproterenol. In particular, both agents increased the phosphorylation of the intermediate filament proteins vimentin and glial fibrillary acidic protein, and decreased the phosphorylation of an unidentified 80 kD protein. Preliminary experiments seem to indicate that, as in the case of cyclic AMP levels, gp 120 partially counteracted the effect of isoproterenol.

CONCLUSIONS: Our data suggest that gp120 interacts with astroglial beta-adrenergic receptors; interaction with astroglial beta-adrenergic receptors may affect the release of neuroactive substances such as taurine, which is modulated by the activation of these receptors.

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