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Type: Journal article
Title: Nedd4-WW domain-binding protein 5 (Ndfip1) is associated with neuronal survival after acute cortical brain injury
Author: Sang, Q.
Kim, M.
Kumar, S.
Bye, N.
Morganti-Kossmann, M.
Gunnersen, J.
Fuller, S.
Howitt, J.
Hyde, L.
Beissbarth, T.
Scott, H.
Silke, J.
Tan, S.
Citation: The Journal of Neuroscience, 2006; 26(27):7234-7244
Publisher: Soc Neuroscience
Issue Date: 2006
ISSN: 0270-6474
Statement of
Qian Sang, Mary H. Kim, Sharad Kumar, Nicole Bye, Maria C. Morganti-Kossman, Jenny Gunnersen, Stephanie Fuller, Jason Howitt, Lavinia Hyde, Tim Beissbarth, Hamish S. Scott, John Silke, and Seong-Seng Tan
Abstract: Understanding the transcriptional response to neuronal injury after trauma is a necessary prelude to formulation of therapeutic strategies. We used Serial Analysis of Gene Expression (SAGE) to identify 50,000 sequence tags representing 18,000 expressed genes in the cortex 2 h after traumatic brain injury (TBI). A similar tag library was obtained from sham-operated cortex. The SAGE data were validated on biological replicates using quantitative real-time-PCR on multiple samples at 2, 6, 12, and 24 h after TBI. This analysis revealed that the vast majority of genes showed a downward trend in their pattern of expression over 24 h. This was confirmed for a subset of genes using in situ hybridization and immunocytochemistry on brain sections. Of the overexpressed genes in the trauma library, Nedd4-WW (neural precursor cell expressed, developmentally downregulated) domain-binding protein 5 (N4WBP5) (also known as Ndfip1) is strongly expressed in surviving neurons around the site of injury. Overexpression of N4WBP5 in cultured cortical neurons increased the number of surviving neurons after gene transfection and growth factor starvation compared with control transfections. These results identify N4WBP5 as a neuroprotective protein and, based on its known interaction with the ubiquitin ligase Nedd4, would suggest protein ubiquitination as a possible survival strategy in neuronal injury.
Keywords: Cerebral Cortex
Mice, Inbred C57BL
Brain Injuries
Acute Disease
Intercellular Signaling Peptides and Proteins
Nerve Growth Factors
Carrier Proteins
Membrane Proteins
Gene Expression Profiling
Reverse Transcriptase Polymerase Chain Reaction
Cell Survival
Gene Library
DOI: 10.1523/JNEUROSCI.1398-06.2006
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