Journal article
The chemokine CXCL12 promotes survival of postmitotic neurons by regulating Rb protein
Cell death and differentiation, v 15(10), pp 1663-1672
Oct 2008
PMID: 18583990
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Postmitotic neurons need to keep their cell cycle under control to survive and maintain a differentiated state. This study aims to test the hypothesis that the chemokine CXCL12 regulates neuronal survival and differentiation by promoting Rb function, as suggested by previous studies showing that CXCL12 protects neurons from apoptosis induced by Rb loss. To this end, the effect of CXCL12 on Rb expression and transcriptional activity and the role of Rb in CXCL12-induced neuronal survival were studied. CXCL12 increases Rb protein and RNA levels in rat cortical neurons. The chemokine also stimulates an exogenous Rb promoter expressed in these neurons and counteracts the inhibition of the Rb promoter induced by E2F1 overexpression. Furthermore CXCL12 stimulates Rb activity as a transcription repressor. The effects of CXCL12 are mediated by its specific receptor CXCR4, and do not require the presence of glia. Finally, shRNA studies show that Rb expression is crucial to the neuroprotective activity of CXCL12 as indicated by NMDA-neurotoxicity assays. These findings suggest that proper CXCR4 stimulation in the mature CNS can prevent impairment of the Rb-E2F pathway and support neuronal survival. This is important to maintain CNS integrity in physiological conditions and prevent neuronal injury and loss typical of many neurodegenerative and neuroinflammatory conditions.
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Details
- Title
- The chemokine CXCL12 promotes survival of postmitotic neurons by regulating Rb protein
- Creators
- M Z Khan - Department of Pharmacology and Physiology, Drexel University College of Medicine, 245 North 15th Street, Philadelphia, PA, USAR Brandimarti - Department of Pharmacology and Physiology, Drexel University College of Medicine, 245 North 15th Street, Philadelphia, PA, USAS Shimizu - Department of Pharmacology and Physiology, Drexel University College of Medicine, 245 North 15th Street, Philadelphia, PA, USAJ Nicolai - Department of Pharmacology and Physiology, Drexel University College of Medicine, 245 North 15th Street, Philadelphia, PA, USAE Crowe - Department of Pharmacology and Physiology, Drexel University College of Medicine, 245 North 15th Street, Philadelphia, PA, USAO Meucci - Department of Pharmacology and Physiology, Drexel University College of Medicine, 245 North 15th Street, Philadelphia, PA, USA
- Publication Details
- Cell death and differentiation, v 15(10), pp 1663-1672
- Publisher
- Springer Nature
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology; Pathology (and Laboratory Medicine)
- Web of Science ID
- WOS:000259219100013
- Scopus ID
- 2-s2.0-52149092335
- Other Identifier
- 991014877822704721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology
- Cell Biology