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Human immunodeficiency virus type 1 Tat protein decreases cyclic AMP synthesis in rat microglia cultures by Mario Patrizio; Mariantonella Colucci; Giulio Levi is a Neuroscience article available to read on EtoBox.

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We have studied the modulation of cyclic AMP (cAMP) accumulation by the human immunodeficiency virus type 1 (HIV 1) protein Tat in microglia and astrocyte cultures obtained from neonatal rat brain. Pretreatment of microglia with recombinant Tat resulted in a dose‐ and time‐dependent decrease of cAMP accumulation induced by subsequent exposure to isoproterenol (1 μm). The inhibitory action of 100 ng/mL Tat approached 50% after 4 h of preincubation and reached a maximum of 70% after 24 h. The Tat‐induced time‐ and dose‐dependent decrease of cAMP accumulation was observed also when microglial cultures were stimulated with the adenylyl cyclase activator forskolin (100 μm). In both cases, Tat inhibitory action was 70% reverted by a specific monoclonal anti‐Tat antibody, but was not prevented either by the phosphodiesterase inhibitor 3‐isobutyl‐1‐methyl‐xantine (100 μm) or by a 16‐h pretreatment of microglial cultures with the Gi protein inhibitor pertussis toxin (10 ng/mL). All these results suggested that the viral protein acts at a step of the cAMP transduction pathway other than receptors, G proteins and phosphodiesterases. The target of Tat appeared to be adenylyl cyclase, whose act

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Author

Mario Patrizio; Mariantonella Colucci; Giulio Levi

Publisher

John Wiley and Sons; Wiley (Blackwell Publishing); Blackwell Publishing Inc.; Wiley (ISSN 0022-3042)

Published

2001

Language

EN

Field

Neuroscience (Life Sciences)