A systems biology strategy to identify molecular mechanisms of action and protein indicators of traumatic brain injury
| Autor: | Kara Schmid, Jacob D. Feala, Bhaskar Dutta, Anders Wallqvist, Xueping Yu, Angela M. Boutté, Chenggang Yu, Jaques Reifman, Jitendra R. Dave, Gregory J. Tawa |
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| Rok vydání: | 2014 |
| Předmět: |
Male
Nervous system Traumatic brain injury Systems biology Nerve Tissue Proteins Nitric Oxide Synthase Type I Biology protein–protein interaction networks Rats Sprague-Dawley Synapse Cellular and Molecular Neuroscience Western blot medicine Animals Research Articles Regulation of gene expression medicine.diagnostic_test Systems Biology traumatic brain injury Intracellular Signaling Peptides and Proteins Membrane Proteins biomarkers medicine.disease Rats pathway analysis Disease Models Animal medicine.anatomical_structure Gene Expression Regulation Membrane protein Brain Injuries Disks Large Homolog 4 Protein Postsynaptic density Neuroscience |
| Zdroj: | Journal of Neuroscience Research |
| ISSN: | 1097-4547 0360-4012 |
| Popis: | The multifactorial nature of traumatic brain injury (TBI), especially the complex secondary tissue injury involving intertwined networks of molecular pathways that mediate cellular behavior, has confounded attempts to elucidate the pathology underlying the progression of TBI. Here, systems biology strategies are exploited to identify novel molecular mechanisms and protein indicators of brain injury. To this end, we performed a meta-analysis of four distinct high-throughput gene expression studies involving different animal models of TBI. By using canonical pathways and a large human protein-interaction network as a scaffold, we separately overlaid the gene expression data from each study to identify molecular signatures that were conserved across the different studies. At 24 hr after injury, the significantly activated molecular signatures were nonspecific to TBI, whereas the significantly suppressed molecular signatures were specific to the nervous system. In particular, we identified a suppressed subnetwork consisting of 58 highly interacting, coregulated proteins associated with synaptic function. We selected three proteins from this subnetwork, postsynaptic density protein 95, nitric oxide synthase 1, and disrupted in schizophrenia 1, and hypothesized that their abundance would be significantly reduced after TBI. In a penetrating ballistic-like brain injury rat model of severe TBI, Western blot analysis confirmed our hypothesis. In addition, our analysis recovered 12 previously identified protein biomarkers of TBI. The results suggest that systems biology may provide an efficient, high-yield approach to generate testable hypotheses that can be experimentally validated to identify novel mechanisms of action and molecular indicators of TBI. |
| Databáze: | OpenAIRE |
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