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Author Lungu, Gina F. ♦ Stoica, George ♦ Wong, Paul K. Y.
Source SpringerLink
Content type Text
Publisher Springer-Verlag
File Format PDF
Copyright Year ©2008
Language English
Subject Domain (in DDC) Technology ♦ Medicine & health
Subject Keyword CVE cells ♦ HIF-1α ♦ Jab1 ♦ MoMuLV-ts1 ♦ neuronal degeneration ♦ p53 ♦ VEGF ♦ Neurosciences ♦ Virology ♦ Infectious Diseases ♦ Immunology ♦ Neurology
Abstract 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)-1α, 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-1α to accelerate its degradation. A rapid degradation of HIF-1α 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-1α, 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-1α, with a final target on VEGF expression and neuronal degeneration.
ISSN 13550284
Age Range 18 to 22 years ♦ above 22 year
Educational Use Research
Education Level UG and PG
Learning Resource Type Article
Publisher Date 2008-01-01
Publisher Place New York
e-ISSN 15382443
Journal Journal of NeuroVirology
Volume Number 14
Issue Number 3
Page Count 13
Starting Page 239
Ending Page 251


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Source: SpringerLink