Journal
JOURNAL OF PROTEOME RESEARCH
Volume 6, Issue 9, Pages 3491-3500Publisher
AMER CHEMICAL SOC
DOI: 10.1021/pr070108e
Keywords
quantitative proteomics; neuroregeneration; neurodegeneration; hippocampus; astrocytes; brain injury; 14-3-3 protein; isoform; FTICR mass spectrometry
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Activation of astrocytes accompanies many brain pathologies. Reactive astrocytes have a beneficial role in acute neurotrauma but later on might inhibit regeneration. 2D-gel electrophoresis and mass spectrometry were applied to study the proteome difference in denervated hippocampus in wildtype mice and mice lacking intermediate filament proteins glial fibrillary acidic protein (GFAP) and vimentin (GFAP(-/-)Vim(-/-)) that show attenuated reactive gliosis and enhanced posttraumatic regeneration. Proteomic data and immunohistochemical analyses showed upregulation of the adapter protein 14-3-3 four days postlesion and suggested that 14-3-3 upregulation after injury is triggered by reactive gliosis. Culture-derived isotope tags (CDIT) and mass spectrometry demonstrated that 14-3-3 epsilon was the major isoform upregulated in denervated hippocampus and that its upregulation was attenuated in GFAP(-/-)Vim(-/-) mice and thus most likely connected to reactive gliosis.
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