title: Response of cell cycle proteins to neurotrophic factor and chemokine stimulation in human neuroglia.
abstract: Increased expression of neurotrophins (e.g., NGF, BDNF) and chemokines (e.g., RANTES) has been observed in neurodegenerative diseases. We examined the effect of these factors on intracellular signaling cascades inducing cell cycle proteins p53, pRb, and E2F1 in human fetal mixed neuronal and glial cells. Comparing neurotrophin- and chemokine-treated cultures with untreated controls showed altered subcellular localization and expression of hyperphosphorylated retinoblastoma protein (ppRb), E2F1, and p53. Using immunofluorescent laser confocal microscopy, E2F1 and ppRb were detected exclusively in neuronal nuclei in control cultures while p53 was cytoplasmic in astrocytes and nuclear in neurons. Following treatment with neurotrophins, E2F1 and ppRb were observed in the cytoplasm of neurons, while p53 was observed in both neuronal and astrocytic nuclei. Similar findings were observed following treatment with RANTES. Semiquantitative analysis using immunoblots showed an increase in the amount of phosphorylated pRb in treated cultures. Induction of cell cycle proteins may play a role in neurodegeneration associated with neurotrophin and chemokine stimulation.
authors.affiliation: Department of Pathology, Division of Neuropathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA. jordan@np.awing.upmc.edu
authors.forename: K L
authors.initials: KL
authors.lastname: Jordan-Sciutto
authors.forename: B A
authors.initials: BA
authors.lastname: Murray Fenner
authors.forename: C A
authors.initials: CA
authors.lastname: Wiley
authors.forename: C L
authors.initials: CL
authors.lastname: Achim
mesh_terms: D001253:Astrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism / Q000494:pharmacology; D002352:Carrier Proteins; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D018946:Chemokine CCL5 / Q000378:metabolism / Q000494:pharmacology; D018925:Chemokines / Q000378:metabolism* / Q000494:pharmacology; D003593:Cytoplasm / Q000378:metabolism; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D006801:Humans; D020932:Nerve Growth Factor / Q000378:metabolism / Q000494:pharmacology; D009414:Nerve Growth Factors / Q000378:metabolism* / Q000494:pharmacology; D009457:Neuroglia / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D016160:Retinoblastoma Protein / Q000378:metabolism; D056465:Retinoblastoma-Binding Protein 1; D015398:Signal Transduction / Q000187:drug effects; D013687:Telencephalon / Q000166:cytology / Q000187:drug effects / Q000196:embryology; D050680:Transcription Factor DP1; D014157:Transcription Factors / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D018946:Chemokine CCL5; D018925:Chemokines; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; D009414:Nerve Growth Factors; D016160:Retinoblastoma Protein; D056465:Retinoblastoma-Binding Protein 1; D050680:Transcription Factor DP1; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D020932:Nerve Growth Factor