Journal article
Expression of the E2F1 transcriptional targets, Cdc2 and PUMA, in primary neurons treated with HIV-gp120 and in the brain of HIV/HAD patients
Journal of neurovirology, Vol.12, pp.74-75
01 May 2006
Abstract
Alterations of the Rb/E2F1 pathway have been involved in neurodegenerative disorders including neuroAIDS. In order to test the hypothesis that an up-regulation of E2F1 activity is involved in HIV neuropathogenesis, we have been studying E2F1 expression and transcriptional activity in primary neurons exposed to HIV-gp120 and in human brain tissue samples from HIV+ patients with or without neurological deficits. Our data show that gp120 induces a time-dependent increase of the E2F1 protein levels in rat primary neurons. In these neurons, E2F1 is predominantly (if not exclusively) localized to the nucleus, and gene reporter assays indicate that gp120 promotes transcription of E2F1-dependent genes. In line with these observations, treatment of neurons with gp120 also increases E2F1 transcriptional targets, namely cdc2 and Puma. Importantly, primary neurons derived from E2F1 deficient mice were resistant to gp120-induced neurotoxicity, and showed no changes in cdc2 and Puma protein levels following gp120 treatment. Finally, the studies with brain tissue samples showed increased expression of E2F1 in the nucleus of neurons of HAD patients, but not in the HIV+ patients without dementia or in control (i.e. HIV negative) patients. These data suggest that aberrant expression of E2F1 transcriptional targets in postmitotic neurons is one of the mechanisms involved in the apoptotic neuronal cell death observed in HIV neuropathology.
Metrics
1 Record Views
Details
- Title
- Expression of the E2F1 transcriptional targets, Cdc2 and PUMA, in primary neurons treated with HIV-gp120 and in the brain of HIV/HAD patients
- Creators
- S ShimizuM KhanR HippensteelO Meucci
- Publication Details
- Journal of neurovirology, Vol.12, pp.74-75
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology
- Identifiers
- 991019170547004721