| First Author | Ballester LY | Year | 2012 |
| Journal | J Biol Chem | Volume | 287 |
| Issue | 5 | Pages | 3079-86 |
| PubMed ID | 22084248 | Mgi Jnum | J:181387 |
| Mgi Id | MGI:5311260 | Doi | 10.1074/jbc.M111.262543 |
| Citation | Ballester LY, et al. (2012) Up-regulation of the neuronal nicotinic receptor alpha7 by HIV glycoprotein 120: potential implications for HIV-associated neurocognitive disorder. J Biol Chem 287(5):3079-86 |
| abstractText | Approximately 30-50% of the >30 million HIV-infected subjects develop neurological complications ranging from mild symptoms to dementia. HIV does not infect neurons, and the molecular mechanisms behind HIV-associated neurocognitive decline are not understood. There are several hypotheses to explain the development of dementia in HIV(+) individuals, including neuroinflammation mediated by infected microglia and neuronal toxicity by HIV proteins. A key protein associated with the neurological complications of HIV, gp120, forms part of the viral envelope and can be found in the CSF of infected individuals. HIV-1-gp120 interacts with several receptors including CD4, CCR5, CXCR4, and nicotinic acetylcholine receptors (nAChRs). However, the role of nAChRs in HIV-associated neurocognitive disorder has not been investigated. We studied the effects of gp120(IIIB) on the expression and function of the nicotinic receptor alpha7 (alpha7-nAChR). Our results show that gp120, through activation of the CXCR4 chemokine receptor, induces a functional up-regulation of alpha7-nAChRs. Because alpha7-nAChRs have a high permeability to Ca(2+), we performed TUNEL staining to investigate the effects of receptor up-regulation on cell viability. Our data revealed an increase in cell death, which was blocked by the selective antagonist alpha-bungarotoxin. The in vitro data are supported by RT-PCR and Western blot analysis, confirming a remarkable up-regulation of the alpha7-nAChR in gp120-transgenic mice brains. Specifically, alpha7-nAChR up-regulation is observed in mouse striatum, a region severely affected in HIV(+) patients. In summary, CXCR4 activation induces up-regulation of alpha7-nAChR, causing cell death, suggesting that alpha7-nAChR is a previously unrecognized contributor to the neurotoxicity associated with HIV infection. |
