Down-regulation of Jab1, HIF-1α, and VEGF by Moloney murine leukemia virus-ts1infection: A possible cause of neurodegeneration

Autor: George Stoica, Paul K.Y. Wong, Gina Lungu
Rok vydání: 2008
Předmět:
Vascular Endothelial Growth Factor A
Endothelium
Down-Regulation
Polymerase Chain Reaction
Neuroprotection
Mice
Cellular and Molecular Neuroscience
chemistry.chemical_compound
Downregulation and upregulation
Virology
Murine leukemia virus
medicine
Animals
Secretion
RNA
Messenger
Cells
Cultured
Mice
Inbred BALB C
Leukemia
Experimental
biology
COP9 Signalosome Complex
Neurodegeneration
Intracellular Signaling Peptides and Proteins
Brain
Hypoxia-Inducible Factor 1
alpha Subunit
medicine.disease
biology.organism_classification
Vascular endothelial growth factor
Tumor Virus Infections
Leukemia
medicine.anatomical_structure
Neurology
chemistry
Nerve Degeneration
Immunology
Cancer research
Endothelium
Vascular
Neurology (clinical)
Moloney murine leukemia virus
Tumor Suppressor Protein p53
Peptide Hydrolases
Protein Binding
Retroviridae Infections
Zdroj: Journal of Neurovirology. 14:239-251
ISSN: 1538-2443
1355-0284
DOI: 10.1080/13550280802093919
Popis: Moloney murine leukemia virus-temperature sensitive (MoMuLV-ts1)-mediated neuronal death is a result of both loss of glial support and release of cytokines and neurotoxins from ts1-infected glial cells. Here the authors propose vascular endothelial growth factor (VEGF) down-regulation as another contributory factor in neuronal degeneration induced by ts1 infection. To determine how ts1 affects VEGF expression in ts1-infected brain, the authors examined the expression of several proteins that are important in regulating the expression of VEGF. The authors found significant decreases in Jun-activating domain-binding protein 1 (Jab1), hypoxia-inducible factor (HIF)-1alpha, and VEGF levels and increases in p53 protein levels in ts1-infected brains compared to noninfected control brains. The authors suggest that a decrease Jab1 expression in ts1 infection leads to accumulation of p53, which binds to HIF-1alpha to accelerate its degradation. A rapid degradation of HIF-1alpha leads to decreased VEGF production and secretion. Considering that endothelial cells are the most conspicuous in virus replication and production in ts1 infection, but are not killed by the infection, the authors examined the expression of these proteins using infected and noninfected mouse cerebrovascular endothelial (CVE) cells. The ts1- infected CVE cells showed decreased Jab1, HIF-1alpha, and VEGF mRNA and protein levels and increased p53 protein levels compared with noninfected cells, consistent with the results found in vivo. These results confirm that ts1 infection results in insufficient secretion of VEGF from endothelial cells and may result in decreased neuroprotection. This study suggested that ts1-mediated neuropathology in mice may result from changes in expression and activity of Jab1, p53, and HIF-1alpha, with a final target on VEGF expression and neuronal degeneration.
Databáze: OpenAIRE
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