Multifaceted role of nitric oxide in an in vitro mouse neuronal injury model: transcriptomic profiling defines the temporal recruitment of death signalling cascades
| Autor: | Minghui Jessica Chen, Zhao Feng Peng, Françoise Russo-Marie, Jayapal Manikandan, Nam Sang Cheung, Philip K. Moore, Guanghou Shui, Matthew Whiteman, Alirio J. Melendez, Philip M Beart |
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| Rok vydání: | 2011 |
| Předmět: |
Time Factors
Cell Survival Molecular Sequence Data Apoptosis Biology Nitric Oxide medicine.disease_cause Nitric oxide Transcriptome Mice chemistry.chemical_compound medicine Animals Cells Cultured Reactive nitrogen species neuronal injury Oligonucleotide Array Sequence Analysis reactive oxygen species Neurons Gene Expression Profiling Computational Biology Original Articles Cell Biology Cell biology Gene expression profiling Nitric oxide synthase Oxidative Stress reactive nitrogen species Gene Expression Regulation chemistry Calcium ion homeostasis biology.protein Molecular Medicine Nitric Oxide Synthase Signal transduction microarray Oxidative stress Signal Transduction |
| Zdroj: | Journal of Cellular and Molecular Medicine |
| ISSN: | 1582-1838 |
| Popis: | Nitric oxide is implicated in the pathogenesis of various neuropathologies characterized by oxidative stress. Although nitric oxide has been reported to be involved in the exacerbation of oxidative stress observed in several neuropathologies, existent data fail to provide a holistic description of how nitrergic pathobiology elicits neuronal injury. Here we provide a comprehensive description of mechanisms contributing to nitric oxide induced neuronal injury by global transcriptomic profiling. Microarray analyses were undertaken on RNA from murine primary cortical neurons treated with the nitric oxide generator DETA-NONOate (NOC-18, 0.5 mM) for 8–24 hrs. Biological pathway analysis focused upon 3672 gene probes which demonstrated at least a ±1.5-fold expression in a minimum of one out of three time-points and passed statistical analysis (one-way anova, P < 0.05). Numerous enriched processes potentially determining nitric oxide mediated neuronal injury were identified from the transcriptomic profile: cell death, developmental growth and survival, cell cycle, calcium ion homeostasis, endoplasmic reticulum stress, oxidative stress, mitochondrial homeostasis, ubiquitin-mediated proteolysis, and GSH and nitric oxide metabolism. Our detailed time-course study of nitric oxide induced neuronal injury allowed us to provide the first time a holistic description of the temporal sequence of cellular events contributing to nitrergic injury. These data form a foundation for the development of screening platforms and define targets for intervention in nitric oxide neuropathologies where nitric oxide mediated injury is causative. |
| Databáze: | OpenAIRE |
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