Journal article
Regulation of neuronal P53 activity by CXCR4
Molecular and cellular neurosciences, v 30(1)
2005
PMID: 16005638
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Abnormal activation of CXCR4 during inflammatory/infectious states may lead to neuronal dysfunction or damage. The major goal of this study was to determine the coupling of CXCR4 to p53-dependent survival pathways in primary neurons. Neurons were stimulated with the HIV envelope protein gp120
IIIB or the endogenous CXCR4 agonist, SDF-1α. We found that gp120 stimulates p53 activity and induces expression of the p53 pro-apoptotic target Apaf-1 in cultured neurons. Inhibition of CXCR4 by AMD3100 abrogates the effect of gp120 on both p53 and Apaf-1. Moreover, gp120 neurotoxicity is markedly reduced by the p53-inhibitor, pifithrin-α. The viral protein also regulates p53 phosphorylation and expression of other p53-responsive genes, such as MDM2 and p21. Conversely, SDF-1α, which can promote neuronal survival, increases p53 acetylation and p21 expression in neurons. Thus, the stimulation of different p53 targets could be instrumental in determining the outcome of CXCR4 activation on neuronal survival in neuroinflammatory disorders.
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Details
- Title
- Regulation of neuronal P53 activity by CXCR4
- Creators
- Muhammad Z Khan - Department of Pharmacology and Physiology, Drexel University College of Medicine, 245 North 15th Street, NCB 8804, Philadelphia, PA 19102, USASaori Shimizu - Department of Pharmacology and Physiology, Drexel University College of Medicine, 245 North 15th Street, NCB 8804, Philadelphia, PA 19102, USAJeegar P Patel - Department of Pharmacology and Physiology, Drexel University College of Medicine, 245 North 15th Street, NCB 8804, Philadelphia, PA 19102, USAAutumn Nelson - Department of Pharmacology and Physiology, Drexel University College of Medicine, 245 North 15th Street, NCB 8804, Philadelphia, PA 19102, USAMy-Thao Le - Department of Pharmacology and Physiology, Drexel University College of Medicine, 245 North 15th Street, NCB 8804, Philadelphia, PA 19102, USAAnna Mullen-Przeworski - Department of Pharmacology and Physiology, Drexel University College of Medicine, 245 North 15th Street, NCB 8804, Philadelphia, PA 19102, USARenato Brandimarti - Department of Experimental Pathology, University of Bologna, Bologna, ItalyAlessandro Fatatis - Department of Pharmacology and Physiology, Drexel University College of Medicine, 245 North 15th Street, NCB 8804, Philadelphia, PA 19102, USAOlimpia Meucci - Department of Pharmacology and Physiology, Drexel University College of Medicine, 245 North 15th Street, NCB 8804, Philadelphia, PA 19102, USA
- Publication Details
- Molecular and cellular neurosciences, v 30(1)
- Publisher
- Elsevier
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology
- Web of Science ID
- WOS:000231439600006
- Scopus ID
- 2-s2.0-23644436050
- Other Identifier
- 991014877802904721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Neurosciences