Neurotoxic effects of the human immunodeficiency virus type-1 transcription factor Tat require function of a polyamine sensitive-site on the N-methyl-d-aspartate receptor

Status Epilepticus-Induced Somatostatinergic Hilar Interneuron Degeneration Is Regulated by Striatal Enriched Protein Tyrosine Phosphatase

“…These findings are consistent with the work of Aarts et al (2002) that reported that nanomolar concentrations of TAT-fusion proteins were not toxic. However, in slice culture, Prendergast et al (2002) did observe TAT-mediated toxicity.…”

The Human Immunodeficiency Virus-1 Protein Transactivator of Transcription Up-Regulates N-Methyl-d-aspartate Receptor Function by Acting at Metabotropic Glutamate Receptor 1 Receptors Coexisting on Human and Rat Brain Noradrenergic Neurones

“…Studies with neuronal and organotypic slice cultures of rat hippocampus, aimed at understanding the mechanisms of NMDAR up-regulation by Tat, reported that the neurotoxicity of the protein may require action at an NMDAR polyamine-sensitive site (Prendergast et al, 2002;Self et al, 2003). These authors found that both the neurotoxicity produced by Tat in the CA1 and CA3 pyramidal cell layers (Prendergast et al, 2002) and the elevations in intracellular Ca 2ϩ caused by the protein in the same regions (Self et al, 2003) could be significantly attenuated by the NMDAR polyamine site antagonist arcaine.…”

“…These authors found that both the neurotoxicity produced by Tat in the CA1 and CA3 pyramidal cell layers (Prendergast et al, 2002) and the elevations in intracellular Ca 2ϩ caused by the protein in the same regions (Self et al, 2003) could be significantly attenuated by the NMDAR polyamine site antagonist arcaine. As shown in Table 2, the potentiation by Tat of the NMDA/glycine-evoked release of [ 3 H]NE in human and rat synaptosomes was insensitive to The Effects of Tat on NMDAR Functions Are Mediated by Activation of a Pertussis Toxin-Sensitive Mechanism.…”

“…Tat has been reported to positively modulate NMDARs in neuronal and organotypic slices (Haughey et al, 2001;Prendergast et al, 2002;Self et al, 2003;Song et al, 2003), but the site of action, whether on NMDARs or on receptive sites that can cross-talk with NMDARs or on both, is not well understood. To shed light on this question, here we investigated whether and how Tat can affect the function of NMDARs known to exist on noradrenergic terminals of human and rat brain.…”

Pathogenesis of Human Immunodeficiency Virus-Induced Neurological Disease

“…Tat is also secreted by infected cells and may induce neuronal death through apoptosis directly, via increases in intracellular calcium thereby stimulating the production of reactive oxygen intermediates and caspase activation; or indirectly, by stimulating macrophages to produce matrix metalloproteinases that induce neuronal apoptosis and whose expression is up-regulated in the brains of patients with HAD (Johnston et al, 2001). Recent evidence suggests that Tat toxicity is dependent upon a polyamine sensitive site on the N-methyl-D-aspartate receptor (Prendergast et al, 2002). In addition, it has been reported that both Tat and Nef increase production of neurotoxic quinolinic acid, a glutamate receptor agonist (Smith et al, 2001), whereas Vpr may cause apoptosis in human neurons .…”