Journal article
The chemokine receptor CXCR4 regulates cell-cycle proteins in neurons
Journal of neurovirology, v 9(3), pp 300-314
Jun 2003
PMID: 12775414
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Neurons express a variety of chemokine receptors that regulate neuronal signaling and survival, including CXCR4 and CCR5, the two major human immunodeficiency virus (HIV) coreceptors. However, the role of chemokine receptors in HIV neuropathology and neuroinflammatory disorders is still unclear. This study aims to determine whether chemokine receptors regulate the activity of cell-cycle proteins in neurons and evaluate the possibility that alterations of these proteins are involved in HIV neuropathogenesis. The authors studied the effect of the chemokine stromal cell-derived factor (SDF)-1
α
, the natural CXCR4 ligand, and an X4-using variant of gp120 on the activity of cell-cycle proteins involved in neuronal apoptosis and differentiation, such as Rb and E2F-1. Changes in expression, localization, and phosphorylation/activation of Rb and E2F-1 induced by SDF-1
α
(20 nM) gp120
IIIB
(200 pM) were analyzed in primary cultures of rat neurons and in a human cell line expressing recombinant CXCR4. The data indicate that changes in the nuclear and cytosolic levels of Rb—which result in the functional loss of this protein—are associated with apoptosis in hippocampal or cerebellar granule neurons and in cell lines. SDF-1
α
, which is able to rescue these neurons from apoptosis, induces a time-dependent increase of total Rb expression while decreasing the nuclear content of phosphorylated (Ser780/Ser795) Rb and the transcriptional activity of E2F-1. The HIV envelope protein gp120
IIIB
exerts opposite effects at the nuclear level. These data indicate that CXCR4 affects cell-cycle proteins in neurons and raise the possibility that chemokines may contribute to neuronal survival by repressing the activity of E2F-dependent apoptotic genes and maintaining neurons in a highly differentiated and quiescent state. This state may be altered during neuroinflammatory conditions and/or by HIV-derived proteins.
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Details
- Title
- The chemokine receptor CXCR4 regulates cell-cycle proteins in neurons
- Creators
- Muhammad Zafrullah Khan - Department of Pharmacology and Physiology, Drexel University College of Medicine, Philadelphia, Pennsylvania, USARenato Brandimarti - Department of Pharmacology and Physiology, Drexel University College of Medicine, Philadelphia, Pennsylvania, USABrian Joseph Musser - Department of Pharmacology and Physiology, Drexel University College of Medicine, Philadelphia, Pennsylvania, USADanielle Marie Resue - Department of Pharmacology and Physiology, Drexel University College of Medicine, Philadelphia, Pennsylvania, USAAlessandro Fatatis - Department of Pharmacology and Physiology, Drexel University College of Medicine, Philadelphia, Pennsylvania, USAOlimpia Meucci - Department of Pharmacology and Physiology, Drexel University College of Medicine, Philadelphia, Pennsylvania, USA
- Publication Details
- Journal of neurovirology, v 9(3), pp 300-314
- Publisher
- Taylor and Francis
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology
- Web of Science ID
- WOS:000183176100003
- Scopus ID
- 2-s2.0-0038784645
- Other Identifier
- 991014878011304721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Neurosciences
- Virology